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Science 10 November 1995:
Vol. 270. no. 5238, p. 893
DOI:

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The immune response relies on selection and massive expansion of a small number of lymphocytes of appropriate antigenic specificity. Subsequent down-modulation of the response prevents the build-up of large numbers of activated lymphocytes. Unlike activation, down-modulation has been refractory to molecular analysis. Now Waterhouse et al. (p. 985; see the Perspective by Allison, p. 932) suggest that the T cell surface molecule CTLA-4 plays a critical role in negative regulation. Mice lacking CTLA-4 suffer a severe lymphoproliferative disorder and die within weeks of birth; T cells from these animals proliferate spontaneously. Adding further interest, CTLA-4 shares sequence homology with CD28, a surface receptor known to be involved in the stimulatory phase.




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Science. ISSN 0036-8075 (print), 1095-9203 (online)