DIFFERENTIAL REQUIREMENT FOR CD4 HELP IN THE DEVELOPMENT OF AN ANTIGEN-SPECIFIC CD8(-CELL RESPONSE DEPENDING ON THE ROUTE OF IMMUNIZATION()T)

Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with syngeneic P815 tumor cells transfected with the HLA-CW3 gen e (P815-CW3) showed a dramatic expansion of activated CD8(+)CD62L(-) T cells expressing exclusively the V@10 segment, We have used this mode l to study the regulatory mechanisms involved in the development of th e CW3-specific CD8(+) response, with respect to different routes of im munization. Whereas both intradermal (i.d.) and i.p. immunization of D BA/2 mice with p815-CW3 cells led to a strong expansion of CD8(+)CD62L (-)V@10(+) cells, only the i.d. route allowed this expansion after imm unization with P815 cells transfected with a minigene coding for the a ntigenic epitope CW3 170-179 (P815 miniCW3), Furthermore, depletion of CD4(+) T cells in vivo completely abolished the specific response of CD8(+)CD62L(-)V@10(+) cells and prevented the rejection of P815-CW3 tu mor cells injected i.p. whereas it did not affect CD8(+)CD62L(-)V@10() cell expansion after i.d. immunization with either P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8(+) memory response was identica l whether or not CD4(+) T cells were depleted during the primary respo nse. Collectively, these results suggest that the CD8(+) T cell respon se to P815-CW3 tumor cells injected i.p. is strictly dependent upon re cognition of a helper epitope by CD4(+) T cells, whereas no such requi rement is observed for i.d. injection.