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CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection

Heath, Sonya L MD; Sabbaj, Steffanie PhD; Bansal, Anju PhD; Kilby, J Michael MD; Goepfert, Paul A MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1st, 2011 - Volume 56 - Issue 3 - p 213-221
doi: 10.1097/QAI.0b013e3181ff2aba
Basic and Translational Science

Understanding the correlates of immunity that control HIV-1 infection is imperative to our understanding of HIV-1 disease and vaccine development. HIV-1-specific cytotoxic T lymphocytes are fundamental to the control of viremia; however, which T-cell repertoire components enact this control remains unclear. We hypothesize that polyfunctional HIV-1-specific CD8 T cells capable of viral control are present in most patients early in infection and these cells are distinguished by their ability to secrete interleukin (IL)-2 and proliferate. We examined HIV-1-specific CD8 T-cell proliferation and cytokine secretion in primary HIV-1 infection (PHI) using known HIV-1 cytotoxic T-cell epitopes to exclude CD4 bystander effect. We found that only a subset of patients with PHI demonstrated “CD4-independent” CD8 proliferation ex vivo. The remainder of the patients lacked HIV-1-specific CD8 T cells with proliferative capacity, even after the addition of exogenous IL-2. Among the proliferators, IL-2 production from the total HIV-specific CD8 T-cell population correlated with proliferation. Surprisingly, though, we did not routinely detect both IL-2 secretion and proliferative capacity from the same antigen-specific CD8 T cells. Thus, there are distinct and heterogeneous populations of CD8 T cells, phenotypically characterized by either proliferation or IL-2 secretion and few with dual capacity. Generation of these responses may be an important measure of HIV-1 control but are not universal after PHI. Furthermore, the heterogeneity of this population suggests that a simple measure of an effective vaccine response remains elusive.

From the *Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; †Department of Medicine, Medical University of South Carolina, Charleston, SC; and ‡Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL.

Received for publication July 21, 2010; accepted September 28, 2010.

Supported by the National Institutes of Health [grants R01 AI084772, R21 AI73103, and R01 AI064060 to P.A.G., AIDERP UO1 A101008 to J.M.K., and MO-RR00032 and P30 AI27767 (CFAR development grant) to S.L.H.], the University of Alabama at Birmingham (Walter B Frommeyer, Jr, Fellowship in Investigative Medicine to S.L.H). This project was also supported by the National Institutes of Health grants 5UL1 RR025777-03 from National Center for Research Resources, 5T36GM73062 from American Society of Physiology, and P30AIO27767 from the University of Alabama at Birmingham, Center for AIDS Research Flow cytometry core.

Portions of this work were presented at the 12th International Congress of Immunology Meeting and the 4th Annual Conference of Federation of Clinical Immunologists Trainee symposium, August 2004, Montreal, Canada and the Proceeding of the Infectious Diseases Society of America, 43rd Annual Meeting, October 2005, San Francisco, CA.

Correspondence to: Sonya L. Heath, CCB 328B, 1530 3rd Avenue South, Birmingham, AL 35294-2050 (e-mail:

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