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Nat Immunol. 2004 Apr;5(4):435-42. Epub 2004 Mar 7.

Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation.

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Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California 94143, USA.


CD28 costimulation is essential for CD4(+) T cell proliferation, survival, interleukin 2 (IL-2) production and T helper type 2 development. To define the nature of the signals that may drive different T cell responses, we have done a structure-function analysis of the CD28 cytoplasmic tail in primary T cells. CD28-mediated T cell proliferation and IL-2 production did not require a particular cytoplasmic domain. In contrast, IL-4 production was driven by the cooperative activity of specific motifs within the CD28 cytoplasmic tail. Using a gene-complementation approach, we provide evidence that one component of this T helper type 2 differentiation signal was mediated by 3-phosphoinositide-dependent protein kinase 1. Thus, different mechanisms underlie the induction of distinct T cell functional responses by CD28.

[Indexed for MEDLINE]

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