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

被引:219
作者
Gea-Banacloche, JC
Migueles, SA
Martino, L
Shupert, WL
McNeil, AC
Sabbaghian, MS
Ehler, L
Prussin, C
Stevens, R
Lambert, L
Altman, J
Hallahan, CW
de Quiros, JCLB
Connors, M
机构
[1] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA
[2] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA
[3] Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
[4] Emory Univ, Vaccine Ctr Yerkes, Atlanta, GA 30322 USA
[5] Hosp Gen Gregorio Maranon, Microbiol Serv, Madrid, Spain
[6] Univ Autonoma Madrid, Serv Med Interne 1, Clin Puerta de Hierro, Madrid, Spain
关键词
D O I
10.4049/jimmunol.165.2.1082
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 how 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-tern 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.
引用
收藏
页码:1082 / 1092
页数:11
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