Transcriptional reprogramming of mature CD4 + helper T cells generates distinct MHC class II- restricted cytotoxic T lymphocytes

2 8 1 CD4 + T cells are commonly classified as 'helper' T cells on the basis of their roles in providing help to promote or dampen cellular and humoral immune responses. In contrast, CD8αβ + cytotoxic T lympho cytes (CTLs) provide direct protective immunity by killing infected or transformed cells. The helper T cell program is initially induced during thymic development, during which thymocytes expressing a major histocompatibility complex (MHC) class II-reactive T cell antigen receptor (TCR) develop into the CD4 + helper T cell lineage, whereas thymocytes with specificity for MHC class I differentiate into the CD8 + CTL lineage. The functional programming, which coincides with but does not depend on the MHC restriction or expression of the coreceptor CD4 or CD8αβ, is controlled by the action and counter action of key transcription factors. Together with Tox and GATA3, the helper T cell transcription factor ThPOK (cKrox; encoded by Zbtb7b (called 'Thpok' here)) first induces the CD4 + helper T cell fate and prevents thymocytes from differentiating into CD8 + CTLs 1-6 . Runx3, a member of the Runx family of transcription factors, has the opposite effect and terminates CD4 expression while promoting differentiation into the CTL lineage That lineage separation, however, is not all encompassing, and reports have repeatedly indicated the presence of CD4 + T cells with cytolytic functions in various species, including humans and rodent

Text and Image: Proceedings of the 61e Rencontre Assyriologique Internationale, Geneva and Bern, 22-26 June 2015

The present volume, number forty in the Series Archaeologica of Orbis Biblicus et Orientalis to appear with the imprint of a new publishing house, the prestigious Uitgeverij Peeters based in Leuven, Belgium. The editors of OBO look forward to this new cooperation and hope that this exceptional volume will be followed by many others during years to come. The 61e Rencontre Assyriologique Internationale was hosted by the Universities of Geneva and Bern and took place 22–26 June 2015. After the 1960 Rencontre in Geneva, this was the second time that the annual conference was held in Switzerland

The Caspase 8 Inhibitor c-FLIP(L) Modulates T-Cell Receptor-Induced Proliferation but Not Activation-Induced Cell Death of Lymphocytes

The caspase 8 inhibitor c-FLIP(L) can act in vitro as a molecular switch between cell death and growth signals transmitted by the death receptor Fas (CD95). To elucidate its function in vivo, transgenic mice were generated that overexpress c-FLIP(L) in the T-cell compartment (c-FLIP(L) Tg mice). As anticipated, FasL-induced apoptosis was inhibited in T cells from the c-FLIP(L) Tg mice. In contrast, activation-induced cell death of T cells in c-FLIP(L) Tg mice was unaffected, suggesting that this deletion process can proceed in the absence of active caspase 8. Accordingly, c-FLIP(L) Tg mice differed from Fas-deficient mice by showing no accumulation of B220(+) CD4(−) CD8(−) T cells. However, stimulation of T lymphocytes with suboptimal doses of anti-CD3 or antigen revealed increased proliferative responses in T cells from c-FLIP(L) Tg mice. Thus, a major role of c-FLIP(L) in vivo is the modulation of T-cell proliferation by decreasing the T-cell receptor signaling threshold