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Interleukin-2 Production by Polyfunctional HIV-1–Specific CD8 T Cells Is Associated With Enhanced Viral Suppression

Akinsiku, Olusimidele T; Bansal, Anju PhD; Sabbaj, Steffanie PhD; Heath, Sonya L MD; Goepfert, Paul A MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1st, 2011 - Volume 58 - Issue 2 - p 132-140
doi: 10.1097/QAI.0b013e318224d2e9
Basic and Translational Science

Background: Assays to measure the induction of HIV-1-specific CD8 T-cell responses often rely on measurements of indirect effector function such as chemokine and cytokine production, which may not reflect direct elimination of an invading pathogen. Assessment of the functional ability of CD8 T cells to suppress HIV-1 replication has been viewed as a surrogate marker of an effectual immune response. To further investigate this, we measured the capacity of virus-specific CD8 T cells to inhibit HIV-1 replication in an in vitro suppression assay.

Methods: We expanded 15 epitope-specific CD8 T-cell lines from peripheral blood mononuclear cells of chronically HIV--infected progressors (n = 5) and controllers (n = 4) who were not on antiretroviral therapy. Cell lines were tested for their ability to produce effector molecules (CD107a, IL-2, IFN-γ, TNF-α, perforin) and suppress virus replication in autologous CD4 T cells.

Results: CD8 T-cell lines from both progressors and controllers had largely similar effector function profiles as determined by intracellular cytokine staining. In contrast, we observed that CD8 T-cell lines derived from controllers show enhanced virus suppression when compared with progressors. Virus suppression was mediated in an major histocompatibility complex-dependent manner and found to correlate with a polyfunctional IL-2+ CD8 T-cell response.

Conclusions: Using a sensitive in vitro suppression assay, we demonstrate that CD8 T-cell-mediated suppression of HIV-1 replication is a marker of HIV-1 control. Suppressive capacity was found to correlate with polyfunctional IL-2 production. Assessment of CD8 T-cell-mediated suppression may be an important tool to evaluate vaccine-induced responses.

From the *Department of Microbiology; and †Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.

Received for publication February 28, 2011; accepted May 16, 2011.

Supported by the National Institutes of Health (NIH) grants R21 AI073103 and R01 AI064060 (awarded to P.A.G.). This work was also supported by the NIH grant P30AIO27767 from the University of Alabama at Birmingham, Center for AIDS Research Clinical and Flow Cytometry Cores.

Presented at Keystone Symposia, HIV Vaccines and Viral Immunity, Banff, March 2010, Alberta, Canada; and at the 10th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS), June 2010, Boston, MA.

The authors have no conflicts of interest to disclose.

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Correspondence to: Paul A. Goepfert, MD, University of Alabama at Birmingham, 908 20th Street South, CCB 328A, Birmingham, AL 35294 (e-mail: paulg@uab.edu).

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