CELLULAR-REQUIREMENTS FOR TUMOR-SPECIFIC IMMUNITY ELICITED BY HEAT-SHOCK PROTEINS - TUMOR REJECTION ANTIGEN-GP96 PRIMES CD8-CELLS IN-VIVO( T)

Purified preparations of 96-kDa heat shock proteins (gp96) have been p reviously shown to elicit tumor-specific immunity to the tumor from wh ich gp96 is obtained but not to antigenically distinct chemically indu ced tumors. The cellular requirements of gp96-elicited immunity have b een examined. It is observed that depletion of CD8+, but not CD4+, T c ells in the priming phase abrogates the immunity elicited by gp96. The CD8+ T cells elicited by immunization with gp96 are active at least u p to 5 weeks after immunization. Depletion of macrophages by treatment of mice with carrageenan during the priming phase also results in los s of gp96-elicited immunity. In the effector phase, all three compartm ents, CD4+ and CD8+ T cells and macrophages, are required. Immunity el icited by whole irradiated tumor cells shows a different profile of ce llular requirements. In contrast to immunization with gp96, depletion of CD4+, but not CD8+, T cells during priming with whole tumor cells a brogates tumor immunity. Further, ablation of macrophage function duri ng priming or effector phases has no effect on tumor immunity elicited by whole cells. Our results suggest the existence of a macrophage-dep endent and a macrophage-independent pathway of tumor immunity. Our obs ervations also show that in spite of exogenous administration, vaccina tion with gp96 preparations elicits a CD8+ T-cell response in vivo, an d it is therefore a useful method of vaccination against cancer and in fectious diseases.