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Unformatted text preview: J OURNAL OF VIROLOGY, June 2008, p. 5398–5407 Vol. 82, No. 11 0022-538X/08/$08.00 1 0 doi:10.1128/JVI.02176-07 Copyright © 2008, American Society for Microbiology. All Rights Reserved. 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 £ Brinda Emu, 1,2 * Elizabeth Sinclair, 2 Hiroyu Hatano, 1 April Ferre, 4 Barbara Shacklett, 4 Jeffrey N. Martin, 3 J. M. McCune, 1,2 and Steven G. Deeks 1 Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California 1 ; Division of Experimental Medicine, University of California, San Francisco, California 2 ; Department of Epidemiology and Biostatistics, University of California, San Francisco, California 3 ; and Department of Microbiology and Immunology, University of California, Davis, California 4 Received 4 October 2007/Accepted 12 March 2008 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 1 and CD8 1 T cells that produce gamma interferon (IFN- g ) 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 HLA-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 1 T cells than those without these alleles ( P 5 0.01). Noncontrollers, with or without protective alleles, had low-level CD8 1 responses. Thus, certain HLA class I alleles are enriched in HIV controllers and are associated with strong Gag-specific CD8 1 IFN- g 1 IL-2 1 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 indi- viduals. Defining mechanisms for virus control in “non-T-cell controllers” might lead to insights into pre- venting HIV transmission or preventing virus replication....
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