The brain parenchyma is permissive for full antitumor CTL effector function, even in the absence of CD4 T cells

Effective antitumor immune responses against cerebral malignancies have bee n demonstrated in several models, but precise cellular function of specific effector cells is poorly understood. We have explored this topic by analyz ing the MHC class I-restricted T cell response elicited after implantation of HLA-CW3-transfected P815 mastocytoma cells (P815-CW3) in syngeneic mice. In this model, tumor-specific CTLs use a distinctive repertoire of TCRs th at allows ex vivo assessment of the response by immunophenotyping and TCR s pectratyping. Thus, for the first time in a brain tumor model, we are able to directly visualize ex vivo CTLs specific for a tumor-expressed Ag, Tumor -specific CTLs are detected in the CNS after intracerebral implantation of P815-CW3, together with other inflammatory cells. Moreover, despite observa tions in other models suggesting that CTLs infiltrating the brain may be fu nctionally compromised and highly dependent upon CD4 T cells, in this synge neic P815-CW3 model, intracerebral tumors were efficiently rejected, whethe r or not CD4 T cells were present. This observation correlated with potent ex vivo cytotoxicity of brain-infiltrating CTLs, specific for the immunodom inant epitope CW3(170-179) expressed on p815-CW3 tumor cells.