SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy
Identifieur interne : 002F61 ( Main/Exploration ); précédent : 002F60; suivant : 002F62SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy
Auteurs : Lucy M. Carruth [États-Unis] ; M. Christine Zink [États-Unis] ; Patrick M. Tarwater [États-Unis] ; Michael D. Miller [États-Unis] ; Ming Li [États-Unis] ; Laurie A. Queen [États-Unis] ; Joseph L. Mankowski [États-Unis] ; Anding Shen [États-Unis] ; Robert F. Siliciano [États-Unis] ; Janice E. Clements [États-Unis]Source :
- Journal of Medical Primatology [ 0047-2565 ] ; 2005-06.
Abstract
Abstract: There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐γ Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.
Url:
DOI: 10.1111/j.1600-0684.2005.00103.x
Affiliations:
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Carruth</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Christine Zink, M" sort="Christine Zink, M" uniqKey="Christine Zink M" first="M." last="Christine Zink">M. Christine Zink</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Tarwater, Patrick M" sort="Tarwater, Patrick M" uniqKey="Tarwater P" first="Patrick M." last="Tarwater">Patrick M. Tarwater</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Biostatistics, University of Texas School of Public Health Houston, El Paso</wicri:cityArea></affiliation></author><author><name sortKey="Miller, Michael D" sort="Miller, Michael D" uniqKey="Miller M" first="Michael D." last="Miller">Michael D. Miller</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Clinical Virology, Gilead Sciences, Inc., Foster City</wicri:cityArea></affiliation></author><author><name sortKey="Li, Ming" sort="Li, Ming" uniqKey="Li M" first="Ming" last="Li">Ming Li</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Queen, Laurie A" sort="Queen, Laurie A" uniqKey="Queen L" first="Laurie A." last="Queen">Laurie A. Queen</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Mankowski, Joseph L" sort="Mankowski, Joseph L" uniqKey="Mankowski J" first="Joseph L." last="Mankowski">Joseph L. Mankowski</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Shen, Anding" sort="Shen, Anding" uniqKey="Shen A" first="Anding" last="Shen">Anding Shen</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><wicri:noRegion>MD</wicri:noRegion></affiliation></author><author><name sortKey="Siliciano, Robert F" sort="Siliciano, Robert F" uniqKey="Siliciano R" first="Robert F." last="Siliciano">Robert F. 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Clements</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Medical Primatology</title><title level="j" type="alt">JOURNAL OF MEDICAL PRIMATOLOGY</title><idno type="ISSN">0047-2565</idno><idno type="eISSN">1600-0684</idno><imprint><biblScope unit="vol">34</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="109">109</biblScope><biblScope unit="page" to="121">121</biblScope><biblScope unit="page-count">13</biblScope><publisher>Munksgaard International Publishers</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-06">2005-06</date></imprint><idno type="ISSN">0047-2565</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0047-2565</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐γ Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li><li>Maryland</li><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Carruth, Lucy M" sort="Carruth, Lucy M" uniqKey="Carruth L" first="Lucy M." last="Carruth">Lucy M. Carruth</name></region><name sortKey="Christine Zink, M" sort="Christine Zink, M" uniqKey="Christine Zink M" first="M." last="Christine Zink">M. Christine Zink</name><name sortKey="Clements, Janice E" sort="Clements, Janice E" uniqKey="Clements J" first="Janice E." last="Clements">Janice E. Clements</name><name sortKey="Li, Ming" sort="Li, Ming" uniqKey="Li M" first="Ming" last="Li">Ming Li</name><name sortKey="Mankowski, Joseph L" sort="Mankowski, Joseph L" uniqKey="Mankowski J" first="Joseph L." last="Mankowski">Joseph L. Mankowski</name><name sortKey="Miller, Michael D" sort="Miller, Michael D" uniqKey="Miller M" first="Michael D." last="Miller">Michael D. Miller</name><name sortKey="Queen, Laurie A" sort="Queen, Laurie A" uniqKey="Queen L" first="Laurie A." last="Queen">Laurie A. Queen</name><name sortKey="Shen, Anding" sort="Shen, Anding" uniqKey="Shen A" first="Anding" last="Shen">Anding Shen</name><name sortKey="Siliciano, Robert F" sort="Siliciano, Robert F" uniqKey="Siliciano R" first="Robert F." last="Siliciano">Robert F. Siliciano</name><name sortKey="Tarwater, Patrick M" sort="Tarwater, Patrick M" uniqKey="Tarwater P" first="Patrick M." last="Tarwater">Patrick M. Tarwater</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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