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HIV-1 Tat Suppresses gp120-Specific T Cell Response in IL-10-Dependent Manner¹

National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune, India

A large number of multicomponent vaccine candidates are currently in clinical evaluation, many of which also include the HIV-1 Tat protein, an important regulatory protein of the virus. However, whether Tat, a known immune effector molecule with a well-conserved sequence among different HIV subtypes, affects the immune response to a coimmunogen is not well understood. In this study, using a bicistronic vector expressing both gp120 and Tat, we have analyzed the role of Tat in elicitation of the gp120-specific immune response. The T cell responses to gp120 were greatly diminished in mice coimmunized with Tat as compared with mice immunized with gp120 alone. This immunosuppressive activity of Tat was not confined to viral Ag only because it also suppressed the immune response of unrelated Ag. Analysis of the cytokine profile suggests that Tat induces IL-10 and since IL-10 has been demonstrated to have appreciable T cell inhibitory activity, it is plausible that IL-10 could be responsible for Tat-mediated immunosuppression. Finally, the immunosuppressive effect of Tat was not observed in IL-10-deficient mice, confirming the role of IL-10 in Tat-mediated immunosuppression. Thus, our results demonstrate for the first time that the immunosuppressive effect of Tat is mediated through IL-10 and suggests that Tat-induced IL-10-mediated immune suppression seems to cripple immune surveillance during HIV-1 infection.

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 the Department of Biotechnology, Government of India. S.G. is a Senior Research Fellow of the National Centre for Cell Science.

² Address correspondence and reprint requests to Dr. Debashis Mitra or Dr. Bhaskar Saha, National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India. E-mail addresses: dmitra{at}nccs.res.in, dmitra01{at}yahoo.co.in, and sahab{at}nccs.res.in

³ Abbreviation used in this paper: WT, wild type; JAM, just another method.