Brenchley J, Ambrozak D, Karandikar N, Betts M, Kuruppu J, Douek D, Koup R; 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. 217-T.

NIAID, NIH, Bethesda, MD

BACKGROUND: HIV-specific CD8+ T-cell responses play an important role in limiting viral replication and progression to AIDS. Functional defects within this population may be involved in the inability of most individuals to effectively contain viral replication. Here, we examine the ability of HIV-specific CD8+ T cells from 24 HIV seropositive individuals to proliferate in response to antigenic stimulation.METHODS: We utilized intracellular cytokine flow cytometery and CFSE in conjunction with overlapping HIV peptides to study antigen specific proliferation. In order to assess the proliferative history of HIV-specific CD8+ T cells, we measured T-cell Receptor Excision Circles (TREC) within these populations as compared to memory CD8+ lymphocytes. We also measured telomere lengths by sorting specific populations of T-cells then utilized telomere specific peptide nucleic acid kits followed by flow cytometery. Wilcoxon matched pairs test and Spearman's rank tests were used for statistical comparisons.RESULTS: HIV-specific CD8+ T cells could be separated into those that divide, and those that do not divide, based upon dilution of CFSE. Those that fail to divide express CD57, similar to other CD57+ lymphocytes that lack proliferation responses to antigen, mitogen, and/or cytokines. CD57+ CD8+ T cells, HIV-specific and otherwise, contain lower levels of TREC than CD57- memory T cells. The percentage of HIV-specific CD57+ CD8+ T cells does not correlate with viral load or CD4 count.CONCLUSIONS: Proliferation defects observed within the HIV-specific CD8+ T-cell population can be attributed to CD57 expression and, likely, replicative senescence evident by significant lower levels of TREC within CD57+ populations. HIV-specific CD8+ T cells may lose proliferative responses after extensive in vivo activation. Following chronic activation HIV-specific CD8+ T cells may become replicatively senescent, express CD57, and become prone to activation induced apoptosis. This phenomenon is not restricted to HIV infection and may be reflective of normal T-cell development during chronic stimulation, i.e. this may not be an actual defect within the HIV-specific CD8+ T cells.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Anti-HIV Agents
• Antigens, CD57
• Antigens, CD8
• CD4 Lymphocyte Count
• CD8-Positive T-Lymphocytes
• Case-Control Studies
• Cell Adhesion Molecules
• Cell Aging
• HIV
• HIV Antigens
• HIV Core Protein p24
• HIV Infections
• HIV Seropositivity
• T-Lymphocytes
• Viral Load
• immunology

Other ID:

• GWAIDS0024112

UI: 102263736

From Meeting Abstracts