Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates
Identifieur interne : 003077 ( Main/Corpus ); précédent : 003076; suivant : 003078Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates
Auteurs : Roy A. E Bakay ; Kevin L. Boyer ; Curt R. Freed ; Aftab A. AnsariSource :
- Cell Transplantation [ 0963-6897 ] ; 1998.
English descriptors
Abstract
Allogeneic transplantation for the therapy of human Parkinson’s disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson’s disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were either controls operated (n = 6), autografted with adrenal medullary and peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue (n= 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.
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DOI: 10.1016/S0963-6897(97)00165-6
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates</title><author><name sortKey="Bakay, Roy A E" sort="Bakay, Roy A E" uniqKey="Bakay R" first="Roy A. E" last="Bakay">Roy A. E Bakay</name><affiliation><mods:affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</mods:affiliation></affiliation><affiliation><mods:affiliation>Roy A.E. Bakay, M.D., Department of Neurosurgery, The Emory Clinic, 1327 Clifton Rd NE, Atlanta, GA 30322.</mods:affiliation></affiliation></author><author><name sortKey="Boyer, Kevin L" sort="Boyer, Kevin L" uniqKey="Boyer K" first="Kevin L" last="Boyer">Kevin L. Boyer</name><affiliation><mods:affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</mods:affiliation></affiliation></author><author><name sortKey="Freed, Curt R" sort="Freed, Curt R" uniqKey="Freed C" first="Curt R" last="Freed">Curt R. Freed</name><affiliation><mods:affiliation>Department of Medical Pharmacology, University of Colorado Health Science Center, Denver, CO, USA</mods:affiliation></affiliation></author><author><name sortKey="Ansari, Aftab A" sort="Ansari, Aftab A" uniqKey="Ansari A" first="Aftab A" last="Ansari">Aftab A. 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E Bakay</name><affiliation><mods:affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</mods:affiliation></affiliation><affiliation><mods:affiliation>Roy A.E. Bakay, M.D., Department of Neurosurgery, The Emory Clinic, 1327 Clifton Rd NE, Atlanta, GA 30322.</mods:affiliation></affiliation></author><author><name sortKey="Boyer, Kevin L" sort="Boyer, Kevin L" uniqKey="Boyer K" first="Kevin L" last="Boyer">Kevin L. Boyer</name><affiliation><mods:affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</mods:affiliation></affiliation></author><author><name sortKey="Freed, Curt R" sort="Freed, Curt R" uniqKey="Freed C" first="Curt R" last="Freed">Curt R. 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Ansari</name><affiliation><mods:affiliation>Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA,</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Cell Transplantation</title><title level="j" type="abbrev">CTR</title><idno type="ISSN">0963-6897</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998">1998</date><biblScope unit="volume">7</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="109">109</biblScope><biblScope unit="page" to="120">120</biblScope></imprint><idno type="ISSN">0963-6897</idno></series><idno type="istex">C73C551BBF7461E2C72FD3C47BA250D907B28063</idno><idno type="DOI">10.1016/S0963-6897(97)00165-6</idno><idno type="PII">S0963-6897(97)00165-6</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0963-6897</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CNS</term><term>Immunological responses</term><term>Injury and grafting</term><term>Nonhuman primates</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Allogeneic transplantation for the therapy of human Parkinson’s disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson’s disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were either controls operated (n = 6), autografted with adrenal medullary and peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue (n= 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Roy A.E Bakay</name><affiliations><json:string>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</json:string><json:string>Roy A.E. Bakay, M.D., Department of Neurosurgery, The Emory Clinic, 1327 Clifton Rd NE, Atlanta, GA 30322.</json:string></affiliations></json:item><json:item><name>Kevin L Boyer</name><affiliations><json:string>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</json:string></affiliations></json:item><json:item><name>Curt R Freed</name><affiliations><json:string>Department of Medical Pharmacology, University of Colorado Health Science Center, Denver, CO, USA</json:string></affiliations></json:item><json:item><name>Aftab A Ansari</name><affiliations><json:string>Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA,</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Immunological responses</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CNS</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Injury and grafting</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Nonhuman primates</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Allogeneic transplantation for the therapy of human Parkinson’s disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson’s disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were either controls operated (n = 6), autografted with adrenal medullary and peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue (n= 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.</abstract><qualityIndicators><score>8</score><pdfVersion>1.2</pdfVersion><pdfPageSize>596 x 795 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>2537</abstractCharCount><pdfWordCount>5971</pdfWordCount><pdfCharCount>39088</pdfCharCount><pdfPageCount>12</pdfPageCount><abstractWordCount>359</abstractWordCount></qualityIndicators><title>Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates</title><pii><json:string>S0963-6897(97)00165-6</json:string></pii><genre><json:string>research-article</json:string></genre><host><volume>7</volume><pii><json:string>S0963-6897(00)X0022-X</json:string></pii><pages><last>120</last><first>109</first></pages><issn><json:string>0963-6897</json:string></issn><issue>2</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Cell Transplantation</title><publicationDate>1998</publicationDate></host><categories><wos><json:string>MEDICINE, RESEARCH & EXPERIMENTAL</json:string><json:string>TRANSPLANTATION</json:string><json:string>CELL & TISSUE ENGINEERING</json:string><json:string>CELL BIOLOGY</json:string></wos></categories><publicationDate>1998</publicationDate><copyrightDate>1998</copyrightDate><doi><json:string>10.1016/S0963-6897(97)00165-6</json:string></doi><id>C73C551BBF7461E2C72FD3C47BA250D907B28063</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/C73C551BBF7461E2C72FD3C47BA250D907B28063/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/C73C551BBF7461E2C72FD3C47BA250D907B28063/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/C73C551BBF7461E2C72FD3C47BA250D907B28063/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/C73C551BBF7461E2C72FD3C47BA250D907B28063/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1998</date></publicationStmt><notesStmt><note type="content">Section title: Original Contributions</note><note type="content">Fig. 1:</note><note type="content">Fig. 2:</note><note type="content">Fig. 3: Host peripheral blood monocellular subset analysis was performed by flow microfluorometric assay using standard immunohistochemical surface markers. Specimens were obtained pretransplantation and at 3 and 6 mo posttransplantation in these particular monkeys. Examples of a fetal mesencephalic allograft and an adrenal medullary autograft are illustrated. No significant differences were observed.</note><note type="content">Fig. 4: Peripheral blood samples were also tested for natural killer (NK) and lymphokine activated killer (LAK) cell function. Examples of monkeys allograted (RJz) and operated surgical control (RGq) exhibited no major differences in the levels of NK or LAK reactivity.</note><note type="content">Fig. 5: Host peripheral blood samples were tested for the presence of donor-specific cytotoxic T-lymphocyte (CTL) reactivity. An example of an allografted monkey’s results at various times after transplantation is demonstrated. There is no difference from pretransplantation reactivity. Positive control was obtained from in vitro sensitization of donor target cells.</note><note type="content">Table 1: Summary of Range of Immunohistological Reactivity for Mononuclear Cell Surface Markers for Each Experimental Group and Time of Analysis</note><note type="content">Table 2: Lack of Donor-Specific Humoral Sensitization—Mesencephalic Allograft Donor</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates</title><author><persName><forename type="first">Roy A.E</forename><surname>Bakay</surname></persName><affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</affiliation><affiliation>Roy A.E. Bakay, M.D., Department of Neurosurgery, The Emory Clinic, 1327 Clifton Rd NE, Atlanta, GA 30322.</affiliation></author><author><persName><forename type="first">Kevin L</forename><surname>Boyer</surname></persName><affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</affiliation></author><author><persName><forename type="first">Curt R</forename><surname>Freed</surname></persName><affiliation>Department of Medical Pharmacology, University of Colorado Health Science Center, Denver, CO, USA</affiliation></author><author><persName><forename type="first">Aftab A</forename><surname>Ansari</surname></persName><affiliation>Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA,</affiliation></author></analytic><monogr><title level="j">Cell Transplantation</title><title level="j" type="abbrev">CTR</title><idno type="pISSN">0963-6897</idno><idno type="PII">S0963-6897(00)X0022-X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998"></date><biblScope unit="volume">7</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="109">109</biblScope><biblScope unit="page" to="120">120</biblScope></imprint></monogr><idno type="istex">C73C551BBF7461E2C72FD3C47BA250D907B28063</idno><idno type="DOI">10.1016/S0963-6897(97)00165-6</idno><idno type="PII">S0963-6897(97)00165-6</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1998</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Allogeneic transplantation for the therapy of human Parkinson’s disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson’s disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were either controls operated (n = 6), autografted with adrenal medullary and peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue (n= 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Immunological responses</term></item><item><term>CNS</term></item><item><term>Injury and grafting</term></item><item><term>Nonhuman primates</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1998">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity><istex:entity SYSTEM="gr5" NDATA="IMAGE" name="gr5"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>CTR</jid><aid>5128</aid><ce:pii>S0963-6897(97)00165-6</ce:pii><ce:doi>10.1016/S0963-6897(97)00165-6</ce:doi><ce:copyright year="1998" type="full-transfer">Elsevier Science Inc.</ce:copyright></item-info><head><ce:dochead><ce:textfn>Original Contributions</ce:textfn></ce:dochead><ce:title>Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates</ce:title><ce:author-group><ce:author><ce:indexed-name>Bakay</ce:indexed-name><ce:given-name>Roy A.E</ce:given-name><ce:surname>Bakay</ce:surname><ce:cross-ref refid="AFF1">A</ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:author><ce:indexed-name>Boyer</ce:indexed-name><ce:given-name>Kevin L</ce:given-name><ce:surname>Boyer</ce:surname><ce:cross-ref refid="AFF1">A</ce:cross-ref></ce:author><ce:author><ce:indexed-name>Freed</ce:indexed-name><ce:given-name>Curt R</ce:given-name><ce:surname>Freed</ce:surname><ce:cross-ref refid="AFF3">C</ce:cross-ref></ce:author><ce:author><ce:indexed-name>Ansari</ce:indexed-name><ce:given-name>Aftab A</ce:given-name><ce:surname>Ansari</ce:surname><ce:cross-ref refid="AFF2">B</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>A</ce:label><ce:textfn>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>B</ce:label><ce:textfn>Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA,</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>C</ce:label><ce:textfn>Department of Medical Pharmacology, University of Colorado Health Science Center, Denver, CO, USA</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Roy A.E. Bakay, M.D., Department of Neurosurgery, The Emory Clinic, 1327 Clifton Rd NE, Atlanta, GA 30322.</ce:text></ce:correspondence></ce:author-group><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Allogeneic transplantation for the therapy of human Parkinson’s disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson’s disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (<ce:italic>Macaca mulatta</ce:italic>) were either controls operated (<ce:italic>n</ce:italic> = 6), autografted with adrenal medullary and peripheral nerve tissue (<ce:italic>n</ce:italic> = 3), or allografted with fetal mesencephalic tissue (<ce:italic>n</ce:italic>= 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Immunological responses</ce:text></ce:keyword><ce:keyword><ce:text>CNS</ce:text></ce:keyword><ce:keyword><ce:text>Injury and grafting</ce:text></ce:keyword><ce:keyword><ce:text>Nonhuman primates</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates</title></titleInfo><name type="personal"><namePart type="given">Roy A.E</namePart><namePart type="family">Bakay</namePart><affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</affiliation><affiliation>Roy A.E. Bakay, M.D., Department of Neurosurgery, The Emory Clinic, 1327 Clifton Rd NE, Atlanta, GA 30322.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kevin L</namePart><namePart type="family">Boyer</namePart><affiliation>Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Curt R</namePart><namePart type="family">Freed</namePart><affiliation>Department of Medical Pharmacology, University of Colorado Health Science Center, Denver, CO, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aftab A</namePart><namePart type="family">Ansari</namePart><affiliation>Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued><copyrightDate encoding="w3cdtf">1998</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Allogeneic transplantation for the therapy of human Parkinson’s disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson’s disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were either controls operated (n = 6), autografted with adrenal medullary and peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue (n= 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.</abstract><note type="content">Section title: Original Contributions</note><note type="content">Fig. 1: </note><note type="content">Fig. 2: </note><note type="content">Fig. 3: Host peripheral blood monocellular subset analysis was performed by flow microfluorometric assay using standard immunohistochemical surface markers. Specimens were obtained pretransplantation and at 3 and 6 mo posttransplantation in these particular monkeys. Examples of a fetal mesencephalic allograft and an adrenal medullary autograft are illustrated. No significant differences were observed.</note><note type="content">Fig. 4: Peripheral blood samples were also tested for natural killer (NK) and lymphokine activated killer (LAK) cell function. Examples of monkeys allograted (RJz) and operated surgical control (RGq) exhibited no major differences in the levels of NK or LAK reactivity.</note><note type="content">Fig. 5: Host peripheral blood samples were tested for the presence of donor-specific cytotoxic T-lymphocyte (CTL) reactivity. An example of an allografted monkey’s results at various times after transplantation is demonstrated. There is no difference from pretransplantation reactivity. Positive control was obtained from in vitro sensitization of donor target cells.</note><note type="content">Table 1: Summary of Range of Immunohistological Reactivity for Mononuclear Cell Surface Markers for Each Experimental Group and Time of Analysis</note><note type="content">Table 2: Lack of Donor-Specific Humoral Sensitization—Mesencephalic Allograft Donor</note><subject lang="en"><genre>Keywords</genre><topic>Immunological responses</topic><topic>CNS</topic><topic>Injury and grafting</topic><topic>Nonhuman primates</topic></subject><relatedItem type="host"><titleInfo><title>Cell Transplantation</title></titleInfo><titleInfo type="abbreviated"><title>CTR</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199803</dateIssued></originInfo><identifier type="ISSN">0963-6897</identifier><identifier type="PII">S0963-6897(00)X0022-X</identifier><part><date>199803</date><detail type="volume"><number>7</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue pages"><start>83</start><end>226</end></extent><extent unit="pages"><start>109</start><end>120</end></extent></part></relatedItem><identifier type="istex">C73C551BBF7461E2C72FD3C47BA250D907B28063</identifier><identifier type="DOI">10.1016/S0963-6897(97)00165-6</identifier><identifier type="PII">S0963-6897(97)00165-6</identifier><accessCondition type="use and reproduction" contentType="">© 1998Elsevier Science Inc.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science Inc., ©1998</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/C73C551BBF7461E2C72FD3C47BA250D907B28063/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">MEDICINE, RESEARCH & EXPERIMENTAL</classCode><classCode scheme="WOS">TRANSPLANTATION</classCode><classCode scheme="WOS">CELL & TISSUE ENGINEERING</classCode><classCode scheme="WOS">CELL BIOLOGY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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