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, Elizabeth Sinclair, Hiroyu Hatano, April Ferre, Barbara Shacklett, Jeffrey N. Martin, J. M. McCune, Steven G. Deeks

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

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-γ) 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 + 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- γ+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.

Original languageEnglish (US)
Pages (from-to)5398-5407
Number of pages10
JournalJournal of Virology
Volume82
Issue number11
DOIs
StatePublished - Jun 2008

ASJC Scopus subject areas

  • Immunology

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