Nagarkatti M, Seth A, Nagarkatti PS
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. [Journal Article, Research Support, U.S. Gov't, P.H.S.]
Cell Immunol 1988 Sep; 115(2):383-92.
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.
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