B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells [AUTOIMMUNITY]

Follicular regulatory T (T_FR) cells are a newly defined regulatory T cell (Treg) subset that suppresses follicular helper T cell–mediated B cell responses in the germinal center reaction. The precise costimulatory signal requirements for proper T_FR cell differentiation and function are still not known. Using conditional knockout strategies of CD28, we previously demonstrated that loss of CD28 signaling in Tregs caused autoimmunity in mice (termed CD28-Treg mice), characterized by lymphadenopathy, accumulation of activated T cells, and cell-mediated inflammation of the skin and lung. In this study, we show that CD28 signaling is required for T_FR cell differentiation. Treg-specific deletion of CD28 caused a reduction in T_FR cell numbers and function, which resulted in increased germinal center B cells and Ab production. Moreover, residual CD28-deficient T_FR cells showed a diminished suppressive capacity as assessed by their ability to inhibit Ab responses in vitro. Surprisingly, genetic deletion of B cells in CD28-Treg mice prevented the development of lymphadenopathy and CD4⁺ T cell activation, and autoimmunity that mainly targeted skin and lung tissues. Thus, autoimmunity occurring in mice with CD28-deficient Tregs appears to be driven primarily by loss of T_FR cell differentiation and function with resulting B cell–driven inflammation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A2l5ET