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 as well as costimulatory molecules, such as those of the CD28/B7 pathway and relatives of the TNFR gene family. Cytotoxic T lymphocytes specific for cellular antigens are in general primed by professional antigen-presenting cells that indirectly present antigens derived from cells in the periphery. This cross-priming of CD8(+) T cells requires signals provided by CD4(+) T helper cells. Although this dependency on [help' for efficient cytotoxic T lymphocyte 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 that T cell help for cytotoxic T lymphocytes is mediated by CD40-CD40Ligand (L) interactions, most likely through activation of professional antigen-presenting cells that cross-present cellular antigens to these T cells.
Toes
R E
RE
Department of Immunohematology and Blood Bank, University Hospital Leiden, Leiden, AZ, 2333, The Netherlands.
Schoenberger
S P
SP
van der Voort
E I
EI
Offringa
R
R
Melief
C J
CJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism*; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand