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Journal of Virology, November 2005, p. 14169-14178, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14169-14178.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Phenotypic, Functional, and Kinetic Parameters Associated with Apparent T-Cell Control of Human Immunodeficiency Virus Replication in Individuals with and without Antiretroviral Treatment

Brinda Emu,1,2 Elizabeth Sinclair,1,2 David Favre,2 Walter J. Moretto,2 Priscilla Hsue,1 Rebecca Hoh,1 Jeffrey N. Martin,1,3 Douglas F. Nixon,1,2 Joseph M. McCune,1,2 and Steven G. Deeks1*

Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California,1 Gladstone Institute of Virology and Immunology, San Francisco, California,2 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California3

Received 27 May 2005/ Accepted 18 July 2005

The human immunodeficiency virus (HIV)-mediated immune response may be beneficial or harmful, depending on the balance between expansion of HIV-specific T cells and the level of generalized immune activation. The current study utilizes multicolor cytokine flow cytometry to study HIV-specific T cells and T-cell activation in 179 chronically infected individuals at various stages of HIV disease, including those with low-level viremia in the absence of therapy ("controllers"), low-level drug-resistant viremia in the presence of therapy (partial controllers on antiretroviral therapy [PCAT]), and high-level viremia ("noncontrollers"). Compared to noncontrollers, controllers exhibited higher frequencies of HIV-specific interleukin-2-positive gamma interferon-positive (IL-2+ IFN-{gamma}+) CD4+ T cells. The presence of HIV-specific CD4+ IL-2+ T cells was associated with low levels of proliferating T cells within the less-differentiated T-cell subpopulations (defined by CD45RA, CCR7, CD27, and CD28). Despite prior history of progressive disease, PCAT patients exhibited many immunologic characteristics seen in controllers, including high frequencies of IL-2+ IFN-{gamma}+ CD4+ T cells. Measures of immune activation were lower in all CD8+ T-cell subsets in controllers and PCAT compared to noncontrollers. Thus, control of HIV replication is associated with high levels of HIV-specific IL-2+ and IFN-{gamma}+ CD4+ T cells and low levels of T-cell activation. This immunologic state is one where the host responds to HIV by expanding but not exhausting HIV-specific T cells while maintaining a relatively quiescent immune system. Despite a history of advanced HIV disease, a subset of individuals with multidrug-resistant HIV exhibit an immunologic profile comparable to that of controllers, suggesting that functional immunity can be reconstituted with partially suppressive highly active antiretroviral therapy.

* Corresponding author. Mailing address: San Francisco General Hospital, 995 Potrero Avenue, San Francisco, CA 94110. Phone: (415) 476-4082, ext. 404. Fax: (415) 826-8449. E-mail: sdeeks{at}php.ucsf.edu.

Journal of Virology, November 2005, p. 14169-14178, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14169-14178.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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