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Animating Regulatory T cells

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Science  28 Jul 2000:
Vol. 289, Issue 5479, pp. 509
DOI: 10.1126/science.289.5479.509a

The importance of regulatory T lymphocytes in maintaining self-tolerance and suppressing autoimmunity has long been apparent, yet a clear functional definition of these cells remains difficult to pin down. Several reports now provide evidence that CTLA-4—a molecule already established in the down-modulation of immune responses—may operate by the provision of signals to a distinct subset of regulatory T cells.

Using different disease models, Read et al. and Takahashi et al. define comparable CD25+ CD4+ T cells, whose pivotal functions in preventing T cell- mediated pathology depend on the constitutive expression of CTLA-4. These findings bear an interesting similarity to those of Salomon et al. who observed that the CD28/B7 co-stimulatory pathway is required for the development and function of CD25+CD4+ regulatory T cells in a mouse model of diabetes. Collectively, these studies may adjust the way CTLA-4 and CD28 are viewed. Thus, in addition to their direct influence on effector T cell function, CTLA-4 and CD28 may fulfill an equally important role as mediators of signals to those T cells responsible for maintaining the immunological status quo. — SJS

J. Exp. Med. 192, 295 (2000); J. Exp. Med. 192, 303 (2000); Immunity12, 431 (2000).

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