HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bostik, P. Articles by Ansari, A. A. Search for Related Content PubMed PubMed Citation Articles by Bostik, P. Articles by Ansari, A. A.

CD4⁺ T Cells from Simian Immunodeficiency Virus Disease-Resistant Sooty Mangabeys Produce More IL-2 Than Cells from Disease-Susceptible Species: Involvement of p300 and CREB at the Proximal IL-2 Promoter in IL-2 Up-Regulation¹

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322

IL-2 is an important cytokine required for the physiological function of CD4⁺ T cells. Immunological unresponsiveness—anergy— of CD4⁺ T cells is characterized by the inability of these cells to synthesize IL-2. Both progressive HIV infection leading to AIDS in humans and SIV infection in rhesus macaques (RM) are associated with dysregulation of IL-2 synthesis. In certain nonhuman primate species, such as sooty mangabeys (SM), SIV infection does not lead to AIDS. We have shown that this is associated with the resistance of the CD4⁺ T cells from SM to undergo anergy in vitro. In this study, we show that CD4⁺ T cells from SM spontaneously synthesize 2- to 3-fold higher levels of IL-2 than corresponding cells from RM. Proximal IL-2 promoter constructs derived from SM show significantly higher activity than the RM-derived constructs in primary CD4⁺ T cells, which is associated with an element at approximately nt –200. Activity of both constructs was up-regulated by p300 and down-regulated by CREB to a similar degree. Chromatin immunoprecipitation analysis showed significantly higher binding of p300 and lower binding of CREB to the SM promoter in vivo. Two single nucleotide substitutions present in the SM sequence around position –200 and –180 seem to increase the affinity of these sites for the binding of transcription factors, one of which was identified as Oct-1. These unique characteristics of the proximal IL-2 promoter in SM therefore can represent one of the mechanisms contributing to the resistance of these cells to undergo anergy.

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 AI65362 (to P.B.) and R01 AI51994 (to A.A.A.).

² Address correspondence and reprint requests to Dr. Pavel Bostik, Department of Pathology and Laboratory Medicine, Emory University, Woodruff Memorial Building, Room #2337A, 101 Woodruff Circle, Atlanta, GA 30322. E-mail address: Pavel.Bostik{at}emory.edu

³ Abbreviations used in this paper: RM, rhesus macaque; ChIP, chromatin immunoprecipitation; SM, sooty mangabey; NHP, nonhuman primate.