UC San Diego

In T cells, Talin has been shown to be a potent activator of integrins which are known to regulate immune synapse formation and migration through the periphery. Outside of its role in mediating integrin adhesion, the role of Talin in T cells is not well understood. To explore the consequences of Talin deletion in T cells, we examined CD4 -Cre positive Talinfl/fl mice. Here, we show that the majority of T cells in floxed Talin-deficient mice display a previously activated CD44hi phenotype. CD4+CD44hi T cells from floxed Talin-deficient mice produced IL-17 and IFN[gamma], while CD8+CD44+ T cells from floxed Talin- deficient mice produced less TNF[alpha] and IFN[gamma] than their wild-type counterparts Furthermore, CD44hi cells from floxed Talin-deficient mice failed to express surface CTLA-4, a molecule known to inhibit T cell activation. This defect in CTLA-4 expression, however, appeared to be limited to CD44hi T cells, as natural T regulatory cells expressed normal levels of CTLA-4. Together, these results suggest a previously unappreciated role for Talin in regulating immune tolerance through the expression of CTLA-4