Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors.

Abstract

The virus-specific CD8+ T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low levels of plasma viral RNA and strong proliferative responses to HIV Ags. HIV-specific CD8+ T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular IFN-gamma in response to HIV-vaccinia recombinant-infected autologous B cells. Very high frequencies (0.8-18.0%) of circulating CD8+ T cells were found to be HIV specific. High frequencies of HIV-specific CD8+ T cells were not limited to long-term nonprogressors with restriction of plasma virus. No correlation was found between the frequency of HIV-specific CD8+ T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the majority of cases not contained within large monoclonal expansions. These data demonstrate that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8+ T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease.

• Authors: J C Gea-Banacloche, S A Migueles, L Martino, W L Shupert, A C McNeil, M S Sabbaghian, L Ehler, C Prussin, R Stevens, L Lambert, J Altman, C W Hallahan, J C de Quiros, M Connors
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 165 Issue 2 Pg. 1082-92 (Jul 15 2000) ISSN: 0022-1767 [Print] United States
• PMID: 10878387 (Publication Type: Journal Article)

Chemical References

• Epitopes, T-Lymphocyte
• HIV Antigens
• Receptors, Antigen, T-Cell, alpha-beta
• Interferon-gamma

Topics

• Adult
• Amino Acid Sequence
• Cytotoxicity Tests, Immunologic
• Cytotoxicity, Immunologic
• Disease Progression
• Epitopes, T-Lymphocyte (analysis, genetics, immunology)
• Female
• HIV Antigens (immunology)
• HIV Infections (immunology, metabolism, pathology, virology)
• Humans
• Interferon-gamma (metabolism)
• Lymphocyte Count
• Male
• Middle Aged
• Molecular Sequence Data
• Receptors, Antigen, T-Cell, alpha-beta (analysis, genetics)
• T-Lymphocytes, Cytotoxic (immunology, metabolism, virology)