Effect of depletion of p38a and p38beta on gene expression in primary effector CD8+ T cells

p38 MAPK is activated during CD8+ T cell primary response. p38 activation promotes effector CD8+ T cell terminal differentiation but represses MPEC formation. p38a/beta deficient mice possess a similar number of virus-specific effector CD8+ T cells as wildtype counterparts. Meanwhile p38a/beta deletion doesn't influence the clearance of LCMV although it impairs the cytolytic activity of CD8+ T cells. Loss of p38a/beta significantly enhances IL-2-producing Tcm accumulation in mouse spleen with no impact on total memory CD8+ T cell numbers yet. And in line with this, more robust proliferation of memory CD8+ T cells in the secondary response and stronger antigen-specific killing ability in rechallenged mice are resulted from p38a/beta deficiency. These results establish a pivotal role for p38a/beta in skewing MPEC formation toward SLEC differentiation, as well as in suppressing Tcm formation, and thus affecting the recall response. Overall design: To investigate the cooperative function of p38a and p38beta in effector CD8+ T cell differentiation, we immunized p38afl/flp38betafl/fl and p38afl/flp38betafl/flGzmBcre mice with LCMV. At 8th day, splenic Db-GP33-41-tetramer+ CD8+ T cells were sorted by flowcytometry. We then performed gene expression profiling analysis using data obtained from RNA-seq of 8 different mice. Comparative gene expression profiling analysis of RNA-seq data for WT cells and its KO counterparts (p38a-/-p38beta-/-).