Iyasere CA, Tilton JC, Migueles S, Laborico A, Connors M; Conference on Retroviruses and Opportunistic Infections.
9th Conf Retrovir Oppor Infect Feb 24 28 2002 Wash State Conv Trade Cent Seattle Wash Conf Retrovir Oppor Infect 9th 2002 Seattle Wash. 2002 Feb 24-28; 9: abstract no. 216-T.
NIAID, NIH, Bethesda, MD
BACKGROUND: Significant frequencies of HIV-specific CD4+ T cells persist in patients with progressive HIV infection despite their inability to mount HIV-specific proliferative responses. To address this dichotomy between frequency and function of HIV-specific CD4+T cells we investigated the mechanisms underlying loss of proliferative responses in a cohort of patients during therapy interruption.METHODS: 13 patients with progressive disease that maintain significant proliferative responses to p24 antigen on therapy (DELTAcpm 1671-19674) were recruited to study the effects of HIV viremia on HIV-specific CD4+ T cell proliferation. Patients were leukopheresed prior to, during, and after therapy interruption. Responses to gag, pol, and nef overlapping peptide pools and p24, CMV and tetanus antigens were measured using flow cytometric detection of IFN-gamma and CFSE staining. Luminex microsphere beads were used to analyze cytokine production in culture supernatents.RESULTS: In response to peptide pools, higher frequencies of HIV-specific CD4+ T cells were measured than previously recognized; gag (0.29% on therapy vs 0.43% off therapy), pol (0.09% vs 0.09%) and nef (0.11% vs 0.09%). Although HIV-specific CD4+ T cells comprised up to 1.5% of CD4+ T cells off therapy, all HIV-specific proliferative responses were abrogated during viremia. Proliferation to tetanus and CMV antigens were diminished during viremia although decreases were less profound than those to HIV antigens. IL-1, IL-2, IL-4, IL-6, IL-10, and TNF-alpha production in response to HIV antigens were also decreased during viremia. Addition of unlabeled PBMC from the aviremic time point recovered proliferation of CFSE labeled CD4+ T cells from the viremic time point suggesting these cells retain proliferative capacity.CONCLUSIONS: HIV-1 viremia causes a profound suppression of HIV-specific proliferation and cytokine production despite maintenance of HIV-1-specific T cells at frequencies similar to other chronic viral infections. Loss of proliferation is not the cause but rather the result of unrestricted viral replication. These results have important implications for both correlates of protective immunity and immune reconstitution.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- Antigens, CD4
- CD4-Positive T-Lymphocytes
- HIV
- HIV Antigens
- HIV Infections
- HIV Long-Term Survivors
- HIV Seropositivity
- HIV-1
- Humans
- Interleukin-2
- Lymphocyte Activation
- T-Lymphocyte Subsets
- T-Lymphocytes
- Viremia
- immunology
Other ID:
UI: 102264159
From Meeting Abstracts