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Specific Induction of Local Antitumor Effector Cells Mediated in Vivo by the Circulating Lymphocyte Pool¹

Hematology/Oncology Section, Cleveland Veterans Administration Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Wistar rats are specifically resistant to the growth of the chemical carcinogen induced syngeneic tumors, Mc7 and Mc107 sarcoma, after being immunized with s.c. implants of irradiated tumor tissue. The central lymph of such immunized rats contains cells able to systemically transfer resistance against tumor growth to normal or irradiated recipient rats. The thoracic duct lymphocytes (TDL) from tumor immune donors are not directly cytotoxic against tumor targets. However recipients of i.v. infused immune TDL develop cytotoxic activity in the peritoneal cavity when challenged with the immunizing tumor at that site. Although the induction of maximum cytotoxicity is tumor specific, peritoneal lavage cells are cytotoxic against both Mc7 and Mc107 tumor targets in the ⁵¹Cr release assay. Inhibition of cytotoxicity in the assay by addition of unlabeled Mc7 or Mc107 sarcoma cells to labeled tumor targets suggests that there is both specific and nonspecific activity in these peritoneal lavage cells. Resistance to in vivo tumor growth in adoptively immunized recipients of TDL challenged with both Mc7 and Mc107 is specific for the immunizing tumor. However growth of a mixture of Mc7 and Mc107 sarcoma cells is inhibited in recipients of immune TDL. The results support the notion that mediator lymphocytes circulate in tumor immunized rats in a noncytotoxic state, specifically recognize tumor cells at a challenge site, and mediate induction of effector cells locally. These effectors are at least in part nonspecific in their cytotoxic activity.

¹ Supported by Medical Research Service, Cleveland Veterans Administration Medical Center.

² Present address: Department of Medicine, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, Ohio 44106. To whom requests for reprints should be addressed.

Received 12/23/86. Revised 8/ 6/87. Accepted 8/10/87.