Abstract
T lymphocytes play a central role in controlling adaptive immune responses. IL-2 critically regulates
both T cell growth and death and is involved in maintaining peripheral tolerance, but the molecules
involved in these and other IL-2 actions are only partially known. We now provide a comprehensive
compendium of the genes expressed in T cells and of those regulated by IL-2 based on a combination
of DNA microarrays and serial analysis of gene expression (SAGE). The newly identified IL-2 target
genes include many genes previously linked to apoptosis in other cellular systems that may
contribute to IL-2-dependent survival functions. We also studied the mRNA expression of known
regulators of signaling pathways for their induction in response to IL-2 in order to identify potential
novel positive and/or negative feedback regulators of IL-2 signaling. We show that IL-2 regulates
only a limited number of these genes. These include suppressors of cytokine signaling (SOCS) 1,
SOCS2, dual-specificity phosphatase (DUSP) 5, DUSP6 and non-receptor type phosphatase-7
(PTPN7). Additionally, we provide evidence that many genes expressed in T cells locate in
chromosomal clusters, and that select IL-2-regulated genes are located in at least two clusters, one at
5q31, a known cytokine gene cluster, and the other at 6p21.3, a region that contains genes encoding
the tumor necrosis factor (TNF) superfamily members TNF, LT-a and LT-b.
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