Expression of active protein kinase B in T cells perturbs both T and B cell homeostasis and promotes inflammation

The molecular mechanisms that contribute to autoimmunity remain poorly defi ned. While inflammation is considered to be one of the major checkpoints in autoimmune disease progression, very little is known about the initiating events that trigger inflammation. We have studied transgenic mice expressin g the prosurvival molecule protein kinase B/Akt under control of a T cell-s pecific CD2 promoter. In this study, we demonstrate that aged mice develop lymphadenopathy and splenomegaly that result from an accumulation of CD4, C D8, and unexpectedly B cells. An increased proportion of T cells express ac tivation markers, while T cell proliferative responses remain normal. B cel ls are hyperproliferative in response to anti-IgM F(ab')(2) and anti-CD40, and increased IgA and IgG2a were found in the sera. In addition, a profound multiorgan lymphocytic infiltration is observed, and T cells from these mi ce display a defect in Fas-mediated apoptosis, which may be the mechanism u nderlying this phenotype. Therefore, T cell expression of active protein ki nase B can alter T cell homeostasis, indirectly influence B cell homeostasi s, and promote inflammation in vivo.