In studies on the mechanisms of graft destruction by lymphoid cells in vivo, we have found that peritoneal exudates induced by the administration of proteose peptone or thioglycollate are extraordinarily rich sources of specific CTLs detectable in vitro at ratios of effector: target cells of less than 1.0. We have induced tumors in mice of congenic strains and are now maintaining them in tissue culture as well as by serial passage in vivo. The very high CTL activity of peritoneal exudate cells obtained from immune mice is difficult to reconcile with the low levels detectable in spleens and whole blood and with the apparent absence of such activity in lymph nodes. Boosting of spleens in vitro leads to marked increases in CTL activity, though never to the levels found in peritoneal exudate cells. Evidently, the presence of inflammatory stimuli in the peritoneal cavity leads to recruitment of either effector cells or their precursors. These observations call into question the origin and fate of such effector cells. If they do not circulate or are not neutralized, then it may be futile to expect cultured lines or clones of effector cells to perform in vivo. In our studies on the neutralization of tumor cells by immune T cells in vivo (Winn assays), we have found that the effectors show varying degrees of susceptibility to anti-Lyt-1 and anti-Lyt-2 antisera and complement. This variation depends on the source of the effectors and on the time that elapses between immunization and harvesting of the T cells. In studies on the variations among mice of different strains in responsiveness to xenografts, we have found no correlative variation in the ontogenic developments of such responsiveness, though with a small number of strains we observed correlative variations in neonatal responses to the injection of rat spleen cells. Specific objectives for the coming year are: (1) to determine whether or not immunologically specific effector cells, especially cytotoxic T lymphocytes, which are obtained from sites of inflammation, can circulate in vivo and return to other sites of inflammation; (2) to determine whether or not there are non-MHC-restricted helper or effector T lymphocytes in peritoneal exudates of mice that have been immunized with MHC-compatible/non-MHC-incompatible grafts; and (3) to determine the specificity of the response of mice to xenografts, particularly with respect to the development of MHC-specific CTLs in the recipients of such grafts. (TT)

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Immunobiology Study Section (IMB)
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Massachusetts General Hospital
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