Chemotherapy of mice bearing syngeneic tumors with 1,3-bis (2-chloroethyl)-1-nitrosourea is effective only in normal, but not in irradiated or nude, mice: role of L3T4+ (CD4+) and Lyt-2+ (CD8+) T cells.
We earlier demonstrated that treatment of C57BL/6 mice bearing a syngeneic tumor, LSA, with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resulted in over 90% survival of the mice, and 100% of the cured mice rejected secondary rechallenge with the homologous tumor but not with a heterologous syngeneic tumor such as EL-4. In the present study we investigated whether the host's immune system was also essential for successful chemotherapy with BCNU. It was observed that BCNU treatment was effective only in normal tumor-bearing mice (100% survival) but not in irradiated or nude tumor-bearing mice (0% survival), thereby suggesting that the immune system, particularly the T cells, was essential for effective treatment with BCNU. Since BCNU-cured mice lack demonstrable T suppressor (Ts) cells, these mice were next used as a model to investigate the phenotype of the T cells mediating tumor rejection. It was observed that L3T4+ (CD4+) or Lyt-2+ (CD8+) T cells from BCNU-cured mice could provide significant protection (80 and 40% survival, respectively) in irradiated or nude mice but not in normal mice. It was also observed that BCNU-cured LSA mice elicited tumor-specific delayed-type hypersensitivity (DTH) reaction, while, normal mice or LSA tumor-bearing mice failed to elicit DTH reaction. Also, only L3T4+ but not Lyt-2+ T cells from BCNU-cured mice when adoptively transferred into nude mice could elicit a DTH reaction. The present study suggests that for effective chemotherapy against a syngeneic tumor, with a tumoricidal drug such as BCNU, the presence of L3T4+ and Lyt-2+ T cells in the host is essential.
Nagarkatti
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Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Seth
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Nagarkatti
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D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D002330:Carmustine / Q000627:therapeutic use*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude / Q000276:immunology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D002330:Carmustine