HLA class I-restricted T-cell responses may contribute to the control of human immunodeficiency virus infection, but such responses are not always necessary for long-term virus control

被引:184
作者
Emu, Brinda [1 ,2 ]
Sinclair, Elizabeth [2 ]
Hatano, Hiroyu [1 ]
Ferre, April [4 ]
Shacklett, Barbara [4 ]
Martin, Jeffrey N. [3 ]
McCune, J. M. [1 ,2 ]
Decks, Steven G. [1 ]
机构
[1] Univ Calif San Diego, San Francisco Gen Hosp, Dept Med, Posit Hlth Program, San Diego, CA 92110 USA
[2] Univ Calif San Diego, Div Expt Med, San Diego, CA 92110 USA
[3] Univ Calif San Diego, Dept Epidemiol & Biostat, San Diego, CA 92110 USA
[4] Univ Calif Davis, Dept Microbiol & Immunol, Davis, CA 95616 USA
关键词
D O I
10.1128/JVI.02176-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A rare subset of human immunodeficiency virus (HIV-infected individuals maintains undetectable HIV RNA levels without therapy ("elite controllers"). To clarify the role of T-cell responses in mediating virus control, we compared HLA class I polymorphisms and HIV-specific T-cell responses among a large cohort of elite controllers (HIV-RNA < 75 copies/ml), "viremic" controllers (low-level viremia without therapy), "non-controllers" (high-level viremia), and "antiretroviral therapy suppressed" individuals (undetectable HIV-RNA levels on antiretroviral therapy). The proportion of CD4(+) and CD8(+) T cells that produce gamma interferon (IFN-gamma) and interleukin-2 (IL-2) in response to Gag and Pol peptides was highest in the elite and viremic controllers (P < 0.0001). Forty percent of the elite controllers were HLA-B*57 compared to twenty-three percent of viremic controllers and nine percent of noncontrollers (P < 0.001). Other HLA class I alleles more common in elite controllers included HLA-B*13, HLA-B*58, and HILA-B*81 (P < 0.05 for each). Within elite and viremic controller groups, those with protective class I alleles had higher frequencies of Gag-specific CD8(+) T cells than those without these alleles (P = 0.01). Noncontrollers, with or without protective alleles, had low-level CD8(+) responses. Thus, certain HLA class I alleles are enriched in HIV controllers and are associated with strong Gag-specific CD8(+)IFN-gamma+IL-2(+) T cells. However, the absence of evidence of T cell-mediated control in many controllers suggests the presence of alternative mechanisms for viral control in these individuals. Defining mechanisms for virus control in "non-T-cell controllers" might lead to insights into preventing HIV transmission or preventing virus replication.
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页码:5398 / 5407
页数:10
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