Abstract
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.
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Acknowledgements
We thank S.W. Jiang and C. McArthur for technical assistance. Supported by National Institutes of Health (RO1 AI25022 (A.K.A.) and K08 DK62343-01 (P.G.A.)), Howard Hughes Postdoctoral Research Fellowship for Physicians (P.G.A.), Abbott Scholar Award in Rheumatology Research (A.N.) and Rosalind Russell Medical Research Center for Arthritis (A.N., L.K., A.W., A.S. and J.I.).
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Andres, P., Howland, K., Nirula, A. et al. Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation. Nat Immunol 5, 435–442 (2004). https://doi.org/10.1038/ni1044
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DOI: https://doi.org/10.1038/ni1044
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