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Journal of Virology, November 2007, p. 12071-12076, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01261-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Controllers but Not Noncontrollers Maintain CD4 T Cells Coexpressing Three Cytokines{triangledown}

Sunil Kannanganat,1,{dagger} Bill G. Kapogiannis,1,2,3,{dagger} Chris Ibegbu,1 Lakshmi Chennareddi,1 Paul Goepfert,4 Harriet L. Robinson,1 Jeffrey Lennox,3 and Rama Rao Amara1*

Vaccine Research Center, Department of Microbiology and Immunology, Yerkes National Primate Research Center,1 Department of Pediatrics,2 Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, Georgia 30329,3 Department of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 352944

Received 9 June 2007/ Accepted 17 August 2007

Here, we evaluate the cytokine coexpression profiles of human immunodeficiency virus (HIV)-specific CD4 T cells for the expression of the cytokines gamma interferon (IFN-{gamma}), interleukin-2, and tumor necrosis factor alpha. In controllers, CD4 T cells producing three or two cytokines (triple producers and double producers, respectively) represented >50% of the total response. In contrast, in noncontrollers ~75% of responding cells produced only one cytokine (single producers), mostly IFN-{gamma}. Cells producing three cytokines were functionally superior to those producing single cytokines and showed an inverse correlation (P < 0.001) with viral load. These results demonstrate a strong association between the maintenance of highly functional CD4 T cells producing three cytokines and control of HIV-1.

* Corresponding author. Mailing address: Emory University, Microbiology and Immunology, 954 Gatewood Road NE, Atlanta, GA 30329. Phone: (404) 727-8765. Fax: (404) 727-7768. E-mail: rama{at}rmy.emory.edu

{triangledown} Published ahead of print on 29 August 2007.

{dagger} S.K. and B.G.K. contributed equally to this work.

Journal of Virology, November 2007, p. 12071-12076, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01261-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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