GROWTH OF P511 MASTOCYTOMA-CELLS IN BALB C MOUSE-BRAIN ELICITS CTL RESPONSE WITHOUT TUMOR ELIMINATION - A NEW TUMOR-MODEL FOR REGIONAL CENTRAL-NERVOUS-SYSTEM IMMUNITY/

We have developed a murine model to explore the tumor-specific CTL res ponse in the immune-privileged central nervous system using P511 masto cytoma cells, Three strains with varying degrees of histocompatibility to P511 cells (CD-I, allogeneic; BALB/c, minor histoincompatible; DBA /2, syngeneic) received tumor cells (10(4)) into the putamen 7 days af ter cannula implantation, when the blood-brain barrier was functionall y intact, Without exception, tumor formed reproducibly by day 7 in all strains, Tumor rejection occurred in CD-1 but not in BALB/c and DBA/2 mice, Using a flank injection site, both CD-1 and BALB/c, but not DBA /2 mice, ultimately rejected flank tumors. Analysis of tumor-specific CTL in BALB/c spleens revealed that P511 administration into brain or flank elicited similar responses: no fully activated CTL were detectab le but a significantly expanded population of nonkilling precursors of CTL (pCTL) were present, A P511 cell-specific pCTL population was als o identified at the brain tumor site 14 days post-tumor introduction, indicating that pCTL, generated in the periphery, traffic to the tumor site in brain. These data indicate that failure to reject tumor in br ain is neither due to lack of afferent stimulation nor to inability of peripheral effecters (P511 cell-specific pCTL) to reach the tumor sit e. We hypothesize that these effector cells are prevented from develop ing into fully activated CTL by conditions within the central nervous system microenvironment that down-regulate CTL development.