Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors.
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.
Gea-Banacloche
J C
JC
Laboratories ofImmunoregulation and Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Migueles
S A
SA
Martino
L
L
Shupert
W L
WL
McNeil
A C
AC
Sabbaghian
M S
MS
Ehler
L
L
Prussin
C
C
Stevens
R
R
Lambert
L
L
Altman
J
J
Hallahan
C W
CW
de Quiros
J C
JC
Connors
M
M
D000328:Adult; D000595:Amino Acid Sequence; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D005260:Female; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma