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HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses

Owen, Rachel Ea,b; Heitman, John Wa; Hirschkorn, Dale Fa; Lanteri, Marion Ca; Biswas, Hope Ha; Martin, Jeffrey Nc; Krone, Melissa Rc; Deeks, Steven Gc; Norris, Philip Ja,b,d; the NIAID Center for HIV/AIDS Vaccine Immunology

doi: 10.1097/QAD.0b013e3283377a1e
Basic Science

Objective: HIV+ elite controllers are a unique group of rare individuals who maintain undetectable viral loads in the absence of antiretroviral therapy. We studied immune responses in these individuals to inform vaccine development, with the goal of identifying the immune correlates of protection from HIV.

Methods: We compared markers of cellular activation, HIV-specific immune responses and regulatory T (Treg) cell frequencies in four groups of individuals: HIV-negative healthy controls, elite controllers (HIV RNA level <75 copies/ml), individuals on HAART and individuals with HIV RNA level more than 10 000 copies/ml (noncontrollers).

Results: Elite controllers possessed significantly lower levels of activated HIV-specific CD8+ T cells and of recently divided HIV-specific CD4+ T cells than noncontrollers, whereas these differences were not seen in the respective cytomegalovirus-specific T-cell populations. Elite controllers also mounted a stronger and broader cytokine and chemokine response following HIV-specific stimulation than individuals on HAART and noncontrollers. Finally, we found that HAART-suppressed individuals had elevated Treg cell frequencies, whereas elite controllers and noncontrollers maintained normal percentages of Treg cells.

Conclusion: Elite controllers maintain high levels of HIV-specific immune responses with low levels of HIV-specific T-cell activation and do not have elevated Treg cell levels. Based on these data an ideal HIV vaccine would induce strong HIV-specific immune responses whereas minimizing HIV-specific T-cell activation.

aBlood Systems Research Institute, USA

bDepartments of Laboratory Medicine, USA

cEpidemiology and Biostatistics, USA

dMedicine, University of California, San Francisco, California, USA.

Received 29 July, 2009

Revised 21 December, 2009

Accepted 6 January, 2010

Correspondence to Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA 94118, USA. Tel: +1 415 923 5769; fax: +1 415 567 5899; e-mail: pnorris@bloodsystems.org

© 2010 Lippincott Williams & Wilkins, Inc.