CD40L expression by CD8+ T cells is essential for successful rejection of SV40 T antigen expressing tumor cells in the absence of CD4+ T cells

Cytotoxicity is considered to be the main effector function of CD8+ T cells in the immune system. However, we demonstrate here that CD40L, one of the central effector molecules of CD4+ helper T cells, is expressed by a substantial part of human and murine CD8+ T cells after activation. Human central as well as effector memory CD8+ T cells comprise up to 50% CD40L+ cells after polyclonal activation. These CD40L+ CD8+ T cells display a non-cytotoxic phenotype and resemble functionally various distinct CD4+ T helper cell subtypes with respect to expression of IL2 and IFNγ or IL4 as well as with respect to their potential to induce activation of B cells and maturation of DCs in vitro. To investigate the functional relevance of CD40L expression by CD8+ T cells we analyzed a murine anti-tumor response. During the whole course of the response 50% of the tumor-specific CD8+ T cells expressed CD40L. While application of CD40L competent wt CD8+ T cells to Rag1ko mice challenged with the tumor cells prevented the establishment of solid tumors, injection of CD40Lko CD8+ T cells resulted in a non-controlled tumor progression similar to non-treated tumors. Our results disclose an essential functional relevance of CD40L expressed by CD8+ T cells. Particularly in situations where CD4+ T-cell help is diminished, MHC-II antigen presentation is reduced or limited danger signals are present, CD40L+ CD8+ T cells may exert essential helper responsibilities for a competent cellular immune response.