CD40 stimulation accelerates deletion of tumor-specific CD8(+) T cells in the absence of tumor-antigen vaccination.
Previous work has established a role for CD40-mediated signals in eliciting helper-dependent CD8(+) T cell responses. Here we investigated the effects of in vivo CD40 stimulation on the survival and function of tumor-specific CD8(+) T cells in a mouse melanoma model system. We found that agonistic anti-CD40 antibody treatment alone of tumor-bearing mice accelerated the deletion of tumor-antigen-specific T cells. However, long-term survival and function of tumor-antigen-specific T cells could be achieved when viral immunization with tumor antigen and anti-CD40 treatment were combined. This rescue of CD8(+) T cells could not be easily replicated by inflammatory or antigen-specific stimuli alone, demonstrating the specificity of signals that regulate the deletion or survival of tumor-specific T cells. These results demonstrate that opposing effects can be elicited by CD40 stimulation in vivo and suggest the need for caution in using this treatment for cancer patients.
Kedl
R M
RM
Cancer Research Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA. rmkedl@mmm.com
Jordan
M
M
Potter
T
T
Kappler
J
J
Marrack
P
P
Dow
S
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014616:Vaccinia virus
D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D010047:Ovalbumin