Th1 and Th2 cell clones to a poorly immunogenic tumor antigen initiate CD8(+) T cell-dependent tumor eradication in vivo

Although CD8+ T cells play a central role as immune effecters, CD4+ T cells act to control the activation and persistence of the CD8+ T cell response in autoimmune disease, antiviral immunity, and experimental systems with im munogenic model tumor Ag, However, little information is available on the e ffects of CD4+ T cells on the function of endogenous CD8+ T lymphocytes rec ognizing authentic tumor rejection Ag with limited immunogenicity, We repor t here that the prophylactic or postchallenge administration of T helper Th 1-type and Th2-type CD4+ clones specific for an unmutated rejection Ag (mur ine P815AB, resembling tumor-specific shared Ag in humans) leads to the ind uction of P815AB-specific reactivity in vivo and concomitant tumor destruct ion, with quantitative rather than qualitative differences characterizing t he antitumor activity of Th1 vs Th2 cells. Because the transferred CD4+ cel ls lacked direct antitumor activity in vitro and required the de novo gener ation of P815AB-specific CD8+ T cells in vivo, these findings suggest that CD4+ lymphocytes can enhance the ability of host APC to initiate an endogen ous CD8+ T cell response to authentic, poorly immunogenic tumor rejection A g.