CD4+ T lymphocytes play a critical role in antibody production and tumor immunity against simian virus 40 large tumor antigen.

Abstract

The role of CD4+ T lymphocytes in antitumor immunity has been largely attributed to providing signals required for the priming of MHC class I-restricted CD8+ cytotoxic T lymphocytes, and CD8+ cytotoxic T lymphocytes are thought to serve as the predominant mediators of tumor killing in vivo. We decided to evaluate the role of T lymphocyte subsets in tumor immunity induced by recombinant SV40 large tumor antigen (Tag) within an experimental murine pulmonary metastasis model of SV40 Tag-expressing tumors. Studies in BALB/c mice used in vivo depletion of either CD4+ or CD8+ T cells in the induction phase of the immune response to SV40 Tag. These studies indicate that CD4+ T cells but not CD8+ T cells were critical in the production of antibodies to SV40 Tag and in tumor immunity as the result of recombinant SV40 Tag immunization. On the basis of the predominance of the IgG1 isotype in the antibody response to SV40 Tag immunization, Th2 type CD4+ T cells appeared to be involved. SV40 Tag immunization was not as effective in the induction of tumor immunity in therapeutic modalities when compared with the prophylactic setting. Our results suggest that CD4+ T cells, along with antibody responses, play a role in the induction of tumor immunity to a viral-encoded tumor antigen.