Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.
BACKGROUND
Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART.


METHODS
Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state.


RESULTS
Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART.


CONCLUSIONS
There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616, USA.
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D
Verhoeven
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S
Sankaran
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S
Dandekar
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D000068679:Emtricitabine / Q000031:analogs & derivatives; D005434:Flow Cytometry / Q000662:veterinary; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology; D008253:Macaca mulatta; D063065:Organophosphonates / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D000068698:Tenofovir; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D016047:Zalcitabine / Q000031:analogs & derivatives / Q000494:pharmacology
D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D016047:Zalcitabine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C075889:Racivir