Cutting Edge: Caspase-11 Limits the Response of CD8+ T Cells to Low-Abundance and Low-Affinity Antigens

Abstract

Inflammatory caspases, including caspase-11, are upregulated in CD8+ T cells after Ag-specific activation, but little is known about their function in T cells. We report that caspase-11–deficient (Casp11−/−) T cells proliferated more readily in response to low-affinity and low-abundance ligands both in vitro and in vivo due to an increased ability to signal through the TCR. In addition to increased numbers, Casp11−/− T cells had enhanced effector function compared with wild-type cells, including increased production of IL-2 and reduced expression of CD62L. Casp11−/− T cells specific for endogenous Ags were more readily deleted than wild-type cells. These data indicate that caspase-11 negatively regulates TCR signaling, possibly through its ability to regulate actin polymerization, and inhibiting its activity could enhance the expansion and function of low-affinity T cells.