The B lymphocyte–induced maturation protein 1 (Blimp-1) transcriptional repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4+ T cells, Blimp-1-deficient CD4+ T cells proliferated more and produced excess interleukin 2 and interferon-γ but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation.
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We thank H. Gu and Y.-R. Zou for advice and for critical reading of the manuscript; the Calame laboratory for advice; J. Liao for assistance with the mice; and D. Savitsky for help with the DSS colitis experiments. Supported by the National Institutes of Health (RO1 AI50659 and RO1 AI43576 to K.C.).
Primer sequences used for Quantitative PCR. (PDF 10 kb)
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