Bcl-2 and Bim play a critical role in the establishment

and maintenance of the immune system by regulating the survival of lymphocytes by apoptosis. The effect of the interaction www.selleckchem.com/products/Adrucil(Fluorouracil).html of Bcl-2 and Bim is dependent on the cell type and/or is tissue-specific: Bcl-2 promotes the survival of naive T cells [7]. In turn, naive T cells from Bim+/– Bcl-2–/– mice die at an accelerated rate in vitro. Bcl-2 is critical to prevent the pro-apoptotic effects of Bim in naive CD8+ T cells in vivo, but other molecules than Bcl-2 might antagonize Bim in CD4+ cells. Bim controls T cell numbers in the periphery by promoting apoptosis and/or decreasing thymic production. Bim-deficient mice have elevated numbers of normal single-positive T cells in the periphery [8]. Bim is a primary trigger for killing autoreactive B cells during their development [9]. In contrast, Bcl-2

is Selleck H 89 required less for the generation and/or maintenance of memory T cells [7]. Bcl-2 and Bim play a critical role in controlling immune responses by regulating the survival, expansion and contraction of lymphocytes by apoptosis. The majority of activated T cells die at the end of a T cell response. Activated T cells exhibit decreased levels of Bcl-2 at the peak of the T cell response, just before they began to die in vivo [10]. A decrease of the pro-survival protein Bcl-2 contributes to apoptosis of activated T cells [11]. Bim deficiency prevents the death of activated T cells in vitro and in vivo, suggesting that the protective effects of Bcl-2 acts solely to neutralize Bim [11]. Thymocytes can be selected negatively by exposure to anti-CD3 antibody, which aggregates the TCR–CD3 complex and kills the CD4+CD8+ population in vivo and

in vitro. Thymocytes lacking the pro-apoptotic Bim are refractory to TCR ligation-induced killing [12]. Stimulation with the superantigen Staphylococcus enterotoxin B (SEB) activates most T cells that express a variable region (V)-β8 TCR. Addition of SEB to fetal thymic organ cultures deletes most developing TCR Vβ8+ thymocytes. In contrast, Ribonucleotide reductase TCR Vβ8+ escapes apoptosis in SEB-treated thymic lobes from Bim–/– embryos [12]. Lymphocytes from Bim–/– mice were found to be relatively resistant to apoptosis upon BH3-only mimetics compared to those from wild-type mice. The presence of Bim affected apoptosis of regulatory T cells (Treg) differently when compared to CD4+8– thymocytes. The loss of pro-apoptotic Bim rescued Treg cells from intrinsically initiated apoptosis [13]. As well as the role of Bim for apoptosis of Treg cells, the absence of Bim also affects the phenotype and function of Treg cells in a manner that indicates loss of function. An exaggerated response of T lymphocytes to luminal antigens is suggested to increase intestinal inflammation in inflammatory bowel disease (IBD).