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Suppression of T‐cell responsiveness by inducible cAMP early repressor (ICER)
Author(s) -
Bodor Josef,
Feigenbaum Lionel,
Bodorova Jana,
Bare Cathy,
Reitz Marvin S.,
Gress Ronald E.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.6.1053
Subject(s) - biology , repressor , transgene , t cell , chemokine , microbiology and biotechnology , immunology , gene expression , gene , immune system , genetics
Depending on the nature of the costimulation of T lymphocytes, expression of regulatory cytokines and chemokines is either susceptibleor resistant to cyclic AMP (cAMP)‐mediated inhibition. Our data showthat cAMP‐mediated inhibition of endogenously expressed cytokines, which is characteristic for T helper (Th) 1‐ and Th 2‐like phenotypes, correlates with the induction of a potent transcriptional repressor, inducible cAMP early repressor (ICER), in both subsets of T cellsactivated under conditions of suboptimal interleukin‐2 (IL‐2)expression. Importantly, Th‐specific expression of certain chemokinesis also susceptible to cAMP‐mediated transcriptional attenuation. Todetermine whether ICER per se, rather than forskolin‐mediated elevationof intracellular cAMP, is responsible for the observed inhibitoryeffect, we generated transgenic mice expressing ICER under the controlof a lymphocyte‐specific lck promoter. On stimulation, transgenic thymocytes overexpressing ICER exhibited reduced levels of IL‐2 and interferon (IFN)‐γ and failed to express the macrophageinflammatory protein (MIP)‐1α and MIP‐1β genes. Splenic T cellsfrom ICER‐transgenic mice showed a defect in proliferation and lacked amixed lymphocyte reaction response, implying that ICER‐mediatedinhibition of cytokine and chemokine expression might play an importantrole in T‐cell inactivation.