CD40-CD40Ligand interactions and their role in cytotoxic T lymphocyte priming and anti-tumor immunity

Tumor-specific immunity relies on interactions with the antigen receptors a s well as costimulatory molecules, such as those of the CD28/B7 pathway and relatives of the TNFR gene family. Cytotoxic T lymphocytes specific for ce llular antigens are in general primed by professional antigen-presenting ce lls that indirectly present antigens derived from cells in the periphery. T his cross-priming of CD8(+) T cells requires signals provided by CD4(+) T h elper cells. Although this dependency on 'help' for efficient cytotoxic T l ymphocyte priming has been well documented, it was only recently that more mechanistic insight into the nature of this event has been obtained. In the absence of the CD4(+) T cells, signalling through CD40 can replace 'help' required for priming of these CD8(+) T cells. These observations indicate t hat T cell help for cytotoxic T lymphocytes is mediated by CD40-CD40Ligand (L) interactions, most likely through activation of professional antigen-pr esenting cells that cross-present cellular antigens to these T cells.