Unravelling the mechanisms of help for CD8+ T cell responses.

CD8+ T cells are critically important for immune defense against many viral and bacterial pathogens, and are also key components of cancer immunotherapy. Help from CD4+ T cells is usually essential for optimal CD8+ T cell responses, driving the primary response, the survival of memory cells, and the generation of protective and therapeutic immunity. Understanding the mechanisms of help is thus essential for vaccine design, and for restoring protective immunity in immunosuppressed individuals. Our laboratory has developed an immunization protocol using peptide-pulsed dendritic cells to stimulate help-dependent primary, memory, and secondary CD8+ T cell responses. We have used gene-targeted and T cell receptor transgenic mice to identify two distinct pathways that generate help-dependent and help-independent CD8+ T cell responses, respectively, and are now starting to define the molecular mechanisms underlying these two pathways.