CD40L signaling from CD8+ T cells confers protection against influenza infection

Abstract

CD40L is a principal mediator of a large range of humoral and cellular responses and CD40L-mediated licensing of dendritic cells is known to be necessary for the generation of robust effector and memory CD8+ T cell responses. Although the effects of CD40L when expressed on CD4+ T cells are well studied, its role when expressed on CD8+ T cells remain unclear. We have previously reported that CD40L signaling mediates the induction of IL-12 p70 production in dendritic cells when expressed by CD8+ T cells. However, the role and importance of this mechanism in CD8+ T cell responses during an infection are not known. To investigate the function of CD40L when expressed on CD8+ T cells in an in vivo mouse model, we crossed OT-I CD8+ T cell receptor transgenic mice with CD40L−/− mice to generate OVA-specific CD8+ T cells that are unable to expressed CD40L. By transferring CD8+ T cells from these mice into CD40L-competent mice and using a strain of influenza that expresses the OVA epitope recognized by OT-I CD8+ T cells, we were able to create an influenza mouse model where CD40L signaling is absent only on the responding CD8+ T cells. Our analysis indicates that CD40L signaling by CD8+ T cells confers protection against influenza infection and that this is likely dependent on the ability of CD8+ T cells to induce IL-12 p70 production in a CD40L-dependent manner.