CD28 facilitates the generation of Foxp3(-) cytokine responsive regulatory T cell precursors.

ABSTRACT: The T cell costimulatory molecule CD28 plays an important role in the thymic generation of Foxp3(+) regulatory T cells (Tregs) essential for the maintenance of self-tolerance. In this study, we show that a cell-intrinsic signal from CD28 is involved in the generation of cytokine-responsive Foxp3(-) precursors using studies of mixed bone marrow chimeras as well as TCR-specific generation of Foxp3(+) cells using intrathymic transfer of TCR-transgenic thymocytes expressing a natural Treg TCR. Contrary to a previous report, the analysis of CD28 mutant knockin mice revealed that this cell-intrinsic signal is only partially dependent on the Lck-binding PYAP motif. Surprisingly, even though the absence of CD28 resulted in a 6-fold decrease in thymic Tregs, the TCR repertoires of CD28-deficient an

SUBMITTER: Lio CW 

PROVIDER: S-EPMC2874117 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature