Journal
NATURE IMMUNOLOGY
Volume 6, Issue 2, Pages 152-162Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1160
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Efficient generation of regulatory T cells (T-reg cells) in the thymus requires CD28 costimulation, but it is not known why. Here, molecular mapping of CD28 costimulation showed that T-reg cell generation requires a motif that binds the tyrosine kinase Lck, precisely the same motif that is required for CD28 costimulation of interleukin 2 production. Nevertheless, CD28 costimulation provides more than interleukin 2 to developing T-reg cells, as CD28 costimulation of T cell receptor-signaled double-positive thymocytes induced expression of Foxp3, considered to be the T-reg 'master gene', as well as GITR and CTLA-4, two proteins expressed on T-reg cells. Thus, CD28 costimulation directly signals developing thymocytes to express Foxp3 and to initiate the T-reg cell differentiation program.
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