CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy

Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral cont...

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Veröffentlicht in:Immunity (Cambridge, Mass.) Jg. 45; H. 3; S. 656
Hauptverfasser: Cartwright, Emily K, Spicer, Lori, Smith, S Abigail, Lee, David, Fast, Randy, Paganini, Sara, Lawson, Benton O, Nega, Melon, Easley, Kirk, Schmitz, Joern E, Bosinger, Steven E, Paiardini, Mirko, Chahroudi, Ann, Vanderford, Thomas H, Estes, Jacob D, Lifson, Jeffrey D, Derdeyn, Cynthia A, Silvestri, Guido
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 20.09.2016
Schlagworte:
Animals
Anti-Retroviral Agents - pharmacology
Antibodies, Viral - immunology
Antiretroviral Therapy, Highly Active - methods
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - drug effects
CD8-Positive T-Lymphocytes - immunology
Female
Lymphocyte Depletion - methods
Macaca mulatta
Male
Simian Acquired Immunodeficiency Syndrome - drug therapy
Simian Acquired Immunodeficiency Syndrome - immunology
Simian Acquired Immunodeficiency Syndrome - virology
Simian Immunodeficiency Virus - drug effects
Simian Immunodeficiency Virus - immunology
Viral Load - drug effects
Viral Load - immunology
Viremia - drug therapy
Viremia - immunology
Viremia - virology
Virus Replication - drug effects
Virus Replication - immunology
ISSN:1097-4180, 1097-4180
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Zusammenfassung:Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8(+) lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8-32 week) ART, depletion of CD8(+) lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8(+) T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4(+) T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8(+) T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.
Bibliographie:ObjectType-Article-1
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2016.08.018