Adoptive Immunotherapy against Allogeneic Kidney Grafts in Dogs with Stable Hematopoietic Trichimerism
Identifieur interne : 000646 ( Pmc/Corpus ); précédent : 000645; suivant : 000647Adoptive Immunotherapy against Allogeneic Kidney Grafts in Dogs with Stable Hematopoietic Trichimerism
Auteurs : Scott S. Graves ; William J. Hogan ; Christian Kuhr ; Razvan Diaconescu ; Michael Harkey ; George E. Sale ; Brad Stone ; George E. Georges ; Rainer StorbSource :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [ 1083-8791 ] ; 2008.
Abstract
Dogs given nonmyeloablative conditioning and marrow grafts from two dog leukocyte antigen- (DLA) identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. Here, we used trichimeras to evaluate strategies of adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from two DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy total body irradiation and given a short course of postgrafting immunosuppression. After confirming stable hematopoietic engraftment, a kidney was transplanted from one of the two marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes (PBL) from each kidney donor were then used to sensitize the alternate marrow donor. Donor lymphocyte infusions (DLI) from the sensitized dogs were given to the trichimeric recipients, whereupon chimerism, graft-versus-host disease (GvHD), and kidney rejection were monitored. After DLI, we observed both prompt rejection of the transplanted marrow-donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably, owing to shared minor histocompatibility antigens, host chimerism also disappeared and GvHD in skin, gut, and liver developed. The native kidneys, while showing lymphocytic infiltration, remained functionally normal. The current study demonstrated that under certain experimental conditions, the kidney, an organ ordinarily not involved in graft-versus-host reactions, can be targeted by sensitized donor lymphocytes.
Url:
DOI: 10.1016/j.bbmt.2008.08.005
PubMed: 18940673
PubMed Central: 2603466
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PMC:2603466Le document en format XML
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<author><name sortKey="Graves, Scott S" sort="Graves, Scott S" uniqKey="Graves S" first="Scott S." last="Graves">Scott S. Graves</name>
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<author><name sortKey="Kuhr, Christian" sort="Kuhr, Christian" uniqKey="Kuhr C" first="Christian" last="Kuhr">Christian Kuhr</name>
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<author><name sortKey="Diaconescu, Razvan" sort="Diaconescu, Razvan" uniqKey="Diaconescu R" first="Razvan" last="Diaconescu">Razvan Diaconescu</name>
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<front><div type="abstract" xml:lang="en"><p id="P1">Dogs given nonmyeloablative conditioning and marrow grafts from two dog leukocyte antigen- (DLA) identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. Here, we used trichimeras to evaluate strategies of adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from two DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy total body irradiation and given a short course of postgrafting immunosuppression. After confirming stable hematopoietic engraftment, a kidney was transplanted from one of the two marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes (PBL) from each kidney donor were then used to sensitize the alternate marrow donor. Donor lymphocyte infusions (DLI) from the sensitized dogs were given to the trichimeric recipients, whereupon chimerism, graft-versus-host disease (GvHD), and kidney rejection were monitored. After DLI, we observed both prompt rejection of the transplanted marrow-donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably, owing to shared minor histocompatibility antigens, host chimerism also disappeared and GvHD in skin, gut, and liver developed. The native kidneys, while showing lymphocytic infiltration, remained functionally normal. The current study demonstrated that under certain experimental conditions, the kidney, an organ ordinarily not involved in graft-versus-host reactions, can be targeted by sensitized donor lymphocytes.</p>
</div>
</front>
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<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9600628</journal-id>
<journal-id journal-id-type="pubmed-jr-id">20830</journal-id>
<journal-id journal-id-type="nlm-ta">Biol Blood Marrow Transplant</journal-id>
<journal-title>Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation</journal-title>
<issn pub-type="ppub">1083-8791</issn>
<issn pub-type="epub">1523-6536</issn>
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<article-id pub-id-type="doi">10.1016/j.bbmt.2008.08.005</article-id>
<article-id pub-id-type="manuscript">NIHMS76260</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Adoptive Immunotherapy against Allogeneic Kidney Grafts in Dogs with Stable Hematopoietic Trichimerism</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Graves</surname>
<given-names>Scott S.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hogan</surname>
<given-names>William J.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kuhr</surname>
<given-names>Christian</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Diaconescu</surname>
<given-names>Razvan</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harkey</surname>
<given-names>Michael</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sale</surname>
<given-names>George E.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stone</surname>
<given-names>Brad</given-names>
</name>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Georges</surname>
<given-names>George E.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Storb</surname>
<given-names>Rainer</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024</aff>
<aff id="A2"><label>2</label>
University of Washington School of Medicine, Seattle, WA, 98195</aff>
<aff id="A3"><label>3</label>
Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101-2795</aff>
<author-notes><corresp id="FN1">Corresponding author: Scott S. Graves, Ph.D., Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA 98109-1024, Phone: (206) 667-5267 / FAX: (206) 667-6124, E-mail: <email>sgraves@fhcrc.org</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>8</day>
<month>11</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="ppub"><month>11</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>11</month>
<year>2009</year>
</pub-date>
<volume>14</volume>
<issue>11</issue>
<fpage>1201</fpage>
<lpage>1208</lpage>
<abstract><p id="P1">Dogs given nonmyeloablative conditioning and marrow grafts from two dog leukocyte antigen- (DLA) identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. Here, we used trichimeras to evaluate strategies of adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from two DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy total body irradiation and given a short course of postgrafting immunosuppression. After confirming stable hematopoietic engraftment, a kidney was transplanted from one of the two marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes (PBL) from each kidney donor were then used to sensitize the alternate marrow donor. Donor lymphocyte infusions (DLI) from the sensitized dogs were given to the trichimeric recipients, whereupon chimerism, graft-versus-host disease (GvHD), and kidney rejection were monitored. After DLI, we observed both prompt rejection of the transplanted marrow-donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably, owing to shared minor histocompatibility antigens, host chimerism also disappeared and GvHD in skin, gut, and liver developed. The native kidneys, while showing lymphocytic infiltration, remained functionally normal. The current study demonstrated that under certain experimental conditions, the kidney, an organ ordinarily not involved in graft-versus-host reactions, can be targeted by sensitized donor lymphocytes.</p>
</abstract>
<kwd-group><kwd>marrow transplantation</kwd>
<kwd>multiple donors</kwd>
<kwd>kidney transplant</kwd>
<kwd>canine</kwd>
<kwd>nonmyeloablative</kwd>
<kwd>GvHD</kwd>
</kwd-group>
<contract-num rid="DK1">P30 DK056465-10</contract-num>
<contract-num rid="CA1">P30 CA015704-34</contract-num>
<contract-num rid="CA1">P01 CA078902-10</contract-num>
<contract-sponsor id="DK1">National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK</contract-sponsor>
<contract-sponsor id="CA1">National Cancer Institute : NCI</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>
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