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CD8+ T cell differentiation into effector cells is initiated early after antigen encounter by signals from the T cell antigen receptor and costimulatory molecules. The molecular mechanisms that establish the timing and rate of differentiation however are not defined. Here we show that the RNA binding proteins (RBP) ZFP36 and ZFP36L1 limit the rate of differentiation of activated naïve CD8+ T cells and the potency of the resulting cytotoxic lymphocytes. The RBP function in an early and short temporal window to enforce dependency on costimulation via CD28 for full T cell activation and effector differentiation by directly binding mRNA of NF-κB, Irf8 and Notch1 transcription factors and cytokines, including Il2. Their absence in T cells, or the adoptive transfer of small numbers of CD8+ T cells lacking the RBP, promotes resilience to influenza A virus infection without immunopathology. These findings highlight ZFP36 and ZFP36L1 as nodes for the integration of the early T cell activation signals controlling the speed and quality of the CD8+ T cell response. RNA binding proteins (RBP) have a function in T cell activation and differentiation. Here the authors show that in the absence of two RBPs, ZFP36 and ZFP36L1, T cells acquire more rapidly superior effector capabilities, showing a limiting function for RBP in T cell activation and differentiation. [ABSTRACT FROM AUTHOR]

Stability of differential inclusions defined by locally Lipschitz compact valued mappings is considered. It is shown that if such a differential inclusion is globally asymptotically stable, then, in fact, it is uniformly globally asymptotically stable (with respect to initial states in compacts). This statement is trivial for differential equations, but here we provide the extension to compact- (not necessarily convex-) valued differential inclusions. The main result is presented in a context which is useful for control-theoretic applications: a differential inclusion with two outputs is considered, and the result applies to the property of global error detectability. [ABSTRACT FROM AUTHOR]