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Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101
After Ag activation of naive T cells in vitro, extensive growth and differentiation into effector cells depend upon IL-2. DNA microarray analysis was used to identify IL-2-dependent molecules regulating this process. In this study, we show that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) is expressed by a cytokine-dependent pathway in activated T lymphocytes. IL-2 production by activated CD4+ and CD8+ T cells inversely correlated with Blimp-1 levels as higher IL-2 production was associated with lower Blimp-1 expression. Furthermore, ectopic expression of Blimp-1 by activated T cells inhibited IL-2 production but enhanced granzyme B and CD25 expression. Collectively, these findings indicate that there is a negative feedback regulatory loop in activated T cells such that IL-2 inhibits its own production through induction of Blimp-1 while promoting an effector cell phenotype.
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 Grant AI40114.
2 Address correspondence and reprint requests to Dr. Thomas R. Malek, Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, 1600 Northwest 10th Avenue, Miami, FL 33101. E-mail address: tmalek{at}med.miami.edu
3 Abbreviations used in this paper: WT, wild type; hCD2, human CD2.
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