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Single-Cell Level Response of HIV-Specific and Cytomegalovirus-Specific CD4 T Cells Correlate With Viral Control in Chronic HIV-1 Subtype A Infection

Eller, Michael A. PhD*,†; Eller, Leigh Anne MSc*; Ratto-Kim, Silvia PhD*; Ouma, Benson J. MSc; Lo, Vicky MSc*; de Souza, Mark PhD, MPH§; Guwatudde, David PhD‡,‖; Nails, Barbara MSc*; Michael, Nelson L. MD, PhD*; Wabwire-Mangen, Fred MD, PhD‡,‖; Robb, Merlin L. MD*; Marovich, Mary A. MD*; Sandberg, Johan K. PhD; Currier, Jeffrey R. PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2012 - Volume 61 - Issue 1 - p 9–18
doi: 10.1097/QAI.0b013e31825c1217
Basic and Translational Science

Background and Objective: HIV-1 subtype A is the second most prevalent subtype globally and is associated with reduced viral load, higher CD4 absolute counts, and slower disease progression. To study the possible role of T cells associated with better outcome, we examined CD4 and CD8 T-cell responses against HIV-1 and cytomegalovirus (CMV) in Ugandans infected with subtype A HIV-1.

Methods: T-cell responses were investigated using flow cytometry and novel subtype A variant inclusive peptide (VIP) sets designed for this evaluation. CD4 T-cell responses focused primarily on Gag, whereas CD8 T-cell responses were broadly directed against Gag, gp41, and Nef VIP sets. CD4 T cells primarily responded with interferon (IFN)-γ, whereas CD8 cells were more diverse with degranulation (CD107a), IFN-γ, and macrophage inflammatory protein (MIP)-1β production.

Results: No relationship was observed between CD8 T-cell responses and the HIV-1 load. Similarly, the frequency of CD4 T cells responding to these antigens did not associate with viral control. However, in CD4 T cells responding against Gag or CMV, the IFN-γ intensity, indicative of the production at the single-cell level, was inversely proportional to viral load. No significant relationship was found between T-cell effector/memory phenotype and viral control.

Conclusions: The per cell production of IFN-γ in CD4 T cells responding to HIV-1 or CMV correlated with viral control in chronic HIV-1 subtype A infection. These data suggest that quantitative aspects at the single-cell level may be more important than the frequency of antigen-specific CD4 T cells in HIV-1 subtype A infection control.

*U.S. Military HIV Research Program, Silver Spring, MD

Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden

Makerere University Walter Reed Project, Kampala, Uganda

§Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

Makerere University School of Public Health, Kampala, Uganda.

Correspondence to: Michael A. Eller, PhD, U.S. Military HIV Research Program, 503 Robert Grant Avenue, Silver Spring, MD 20910 (e-mail:

Supported by the U.S. Army Medical Research and Materiel Command and its Cooperative Agreement (W81XWH-04-02-0005) with the Henry M. Jackson Foundation for the Advancement of Military Medicine. This work was also supported by the Swedish Research Council and Karolinska Institutet.

The authors have no conflicts of interest to disclose.

The views and opinions expressed in this study do not necessarily reflect those of the U.S. Army, the Department of Defense.

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Received January 13, 2012

Accepted April 24, 2012

© 2012 Lippincott Williams & Wilkins, Inc.