CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2.
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.
Tai
Xuguang
X
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cowan
Michelle
M
Feigenbaum
Lionel
L
Singer
Alfred
A
D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D018106:CD28 Antigens; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2