Suppression of T cell function: a potential role for transcriptional repressor ICER

In this article, we review the inducible cAMP early repressor (ICER) and its possible critical involvement in modulation of T cell responsiveness by its capacity to transcriptionally attenuate interleukin‐2 (IL‐2) gene expression. It seems clear that the failure to produce the IL‐2 is an important determinant of anergy induction. It is important that the CD28‐responsive element (CD28RE), a composite DNA binding element consisting of NFAT and cyclic AMP‐responsive (CRE)‐like motifs in position of –160 of IL‐2 promoter has the high affinity for ICER binding as well as NFAT/ICER complex formation. Moreover, CD28RE with adjacent DNA sequences was also shown to be essential for conferring anergy in T lymphocytes. Because ICER does not possess a transactivation domain required for the recruitment of CBP/p300, the binding of ICER to CD28RE and/or composite motifs containing CRE‐like DNA motifs may lead to uncoupling of CBP/p300 thus extinguishing IL‐2 expression as well as expression of numerous other cytokines and chemokines. J. Leukoc. Biol. 67: 774–779; 2000.