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Differential Requirement for CD4 Help in the Development of an Antigen-Specific CD8⁺ T Cell Response Depending on the Route of Immunization¹

Hélène Bour^*, Clotilde Horvath^*, Christophe Lurquin, Jean-Charles Cerottini^* and H. Robson MacDonald^2,*

^* Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; and Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium

Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with syngeneic P815 tumor cells transfected with the HLA-CW3 gene (P815-CW3) showed a dramatic expansion of activated CD8⁺CD62L^- T cells expressing exclusively the Vß10 segment. We have used this model to study the regulatory mechanisms involved in the development of the CW3-specific CD8⁺ response, with respect to different routes of immunization. Whereas both intradermal (i.d.) and i.p. immunization of DBA/2 mice with P815-CW3 cells led to a strong expansion of CD8⁺CD62L^-Vß10⁺ cells, only the i.d. route allowed this expansion after immunization with P815 cells transfected with a minigene coding for the antigenic epitope CW3 170–179 (P815 miniCW3). Furthermore, depletion of CD4⁺ T cells in vivo completely abolished the specific response of CD8⁺CD62L^-Vß10⁺ cells and prevented the rejection of P815-CW3 tumor cells injected i.p, whereas it did not affect CD8⁺CD62L^-Vß10⁺ cell expansion after i.d. immunization with either P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8⁺ memory response was identical whether or not CD4⁺ T cells were depleted during the primary response. Collectively, these results suggest that the CD8⁺ T cell response to P815-CW3 tumor cells injected i.p. is strictly dependent upon recognition of a helper epitope by CD4⁺ T cells, whereas no such requirement is observed for i.d. injection.

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