ShcA regulates late stages of T cell development and peripheral CD4+ T cell numbers.

摘要: T cell development in the thymus is a highly regulated process that critically depends upon productive signaling via preTCR at β-selection stage, as well TCR for selection from CD4(+)CD8(+) double-positive stage to CD4 or CD8 single-positive stage. ShcA an adapter protein expressed thymocytes, and it required through preTCR, with impaired leading developmental block checkpoint. However, role of subsequent stages has not been addressed. In this study, we generated transgenic mice (CD4-Cre/ShcFFF mice) specifically express phosphorylation-defective dominant-negative mutant (ShcFFF) late development. Thymocytes CD4-Cre/ShcFFF progressed normally checkpoint, but displayed significant reduction numbers CD4(+) CD8(+) thymocytes. Furthermore, mice, when bred mouse strains, had TCRs. Consistent defective progression also peripheral lymphopenia. Moreover, these develop attenuated disease cell-dependent experimental autoimmune encephalomyelitis, model multiple sclerosis. Collectively, data identify important later thymic events.