Defective Th function induced by a dominant-negative cAMP response element binding protein mutation is reversed by Bcl-2.

Zhang F, Rincon M, Flavell RA, Aune TM
J Immunol. 2000 165 (4): 1762-70

PMID: 10925253 · DOI:10.4049/jimmunol.165.4.1762

cAMP response element binding protein (CREB) is a critical regulator of diverse stimulus-dependent transcriptional events. Following TCR stimulation, CREB is rapidly induced in CD4+ Th cell precursors, but not in effector Th cells. However, its role in mature T cell function is incompletely defined. Transgenic mice expressing a CREB dominant-negative (dn) mutation in the T cell lineage exhibited normal T cell development in the thymus, normal T cell homeostasis in the periphery, and normal T cell clonal expansion following Ag challenge. However, this mutation caused selective inhibition of Th cell function in vitro and in vivo, and increased susceptibility of Th cells to activation-induced cell death. Th cells expressing the CREB-dn mutation contained reduced levels of the inhibitor of programmed cell death, BCL-2; overexpression of BCL-2 in transgenic mice reversed both susceptibility to activation-induced cell death in CREB-dn T cells and the defect in effector cytokine production. Thus, CREB plays a critical role in Th cell function and development of Th cell-mediated adaptive immune responses, at least in part, by inhibiting stimulus-dependent cell death.

MeSH Terms (20)

Alanine Amino Acid Substitution Animals Cell Death Cell Differentiation Cell Division Cyclic AMP Response Element-Binding Protein Homeostasis Interleukin-2 Interphase Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Transgenic Point Mutation Proto-Oncogene Proteins c-bcl-2 Receptors, Antigen, T-Cell Serine T-Lymphocytes, Helper-Inducer Thymus Gland

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