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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901760v1 183/8/5407    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Ali, Z. Articles by Chen, Z. W. PubMed PubMed Citation Articles by Ali, Z. Articles by Chen, Z. W.

T Cell Immune Manipulation during Chronic Phase of Simian HIV Infection Confers Immunological Benefits¹

Zahida Ali,^* Lin Yan,^* Nicholas Plagman, Armin Reichenberg, Martin Hintz, Hassan Jomaa, Francois Villinger, and Zheng W. Chen^2*

^*Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30329; and Institut für Klinische Immunologie und Transfusionsmedizin, Universitätsklinikum Gießen und Marburg, Giessen, Germany

V2V2 T cells, a major human T cell subset, recognize the phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by mycobacteria and some opportunistic pathogens, and they contribute to innate/adaptive/homeostatic and anticancer immunity. As initial efforts to explore V2V2 T cell-based therapeutics against HIV/AIDS-associated bacterial/protozoal infections and neoplasms, we investigated whether a well-defined HMBPP/IL-2 therapeutic regimen could overcome HIV-mediated immune suppression to massively expand polyfunctional V2V2 T cells, and whether such activation/expansion could impact AIDS pathogenesis in simian HIV (SHIV)-infected Chinese rhesus macaques. While HMBPP/IL-2 coadministration during acute or chronic phase of SHIV infection induced massive activation/expansion of V2V2 T cells, the consequences of such activation/expansions were different between these two treatment settings. HMBPP/IL-2 cotreatment during acute SHIV infection did not prevent the increases in peak and set-point viral loads or the accelerated disease progression seen with IL-2 treatment alone. In contrast, HMBPP/IL-2 cotreatment during chronic infection did not exacerbate disease, and more importantly it could confer immunological benefits. Surprisingly, although viral antigenic loads were not increased upon HMBPP/IL-2 cotreatment during chronic SHIV infection, HMBPP activation of V2V2 T cells boosted HIV Env-specific Ab titers. Such increases in Abs were sustained for >170 days and were immediately preceded by increased production of IFN-, TNF-, IL-4, and IL-10 during peak expansion of V2V2 T cells displaying memory phenotypes, as well as the short-term increased effector function of V2V2 T cells and CD4⁺ and CD8⁺ β T cells producing antimicrobial cytokines. Thus, HMBPP/V2V2 T cell-based intervention may potentially be useful for combating neoplasms and HMBPP-producing opportunistic pathogens in chronically HIV-infected individuals.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01 HL64560 and R01 RR13601 (both to Z.W.C.).

² Address correspondence and reprint requests to Dr. Zheng W. Chen, Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois at Chicago, College of Medicine, 835 S. Wolcott Avenue, MC790, Chicago, IL 60612. E-mail address: zchen{at}uic.edu

³ Abbreviations used in this paper: ART, antiretroviral treatment; HMBPP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; SHIV, simian HIV; HAART, highly active antiretroviral treatment.