The ability of cells from mice infected with Trypanosoma cruzi to generate specific as well as nonspecific cell-mediated cytotoxic responses to allogeneic tumor cells was investigated. The capacity of spleen cells from either C3H/He (C3H) or C57BL/6 (B6) mice to develop cytotoxic responses in vitro against P-815 tumor cells was depressed after the 2nd wk of acute infection initiated with 10(3) parasites. However, spleen cell responses in B6 mice sensitized against P-815 were depressed only in those mice infected for 16 to 22 days and were significantly enhanced in mice infected for shorter or longer periods of time. In subsequent experiments, significant cytotoxic activity against P-815 target cells was observed in cells from infected B6 and, to a lesser degree, C3H mice without prior sensitization with the tumor cells. With the use of both P-815 and YAC tumor cell lines in cytotoxicity assays, two phases of apparently nonspecific T. cruzi-induced lytic activity (TILA) were observed after infection: a 1st phase detected within 2 days against YAC target cells, and a subsequent phase detected against both YAC and P-815 target cells at a time dependent upon the number of parasites injected. Other results demonstrated increased cytotoxic activity against P-815 target cells in 2.5-mo-old C3H mice infected with greater numbers of T. cruzi or when older (4.5 to 6.5 mo) mice were infected with 10(3) parasites. Antibodies cross-reactive to tumor cells were not detected in sera from infected mice, suggesting that TILA is an antibody-independent phenomenon. Possible relationships between the phases of TILA and the modification of specific responses generated in infected mice are discussed.

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