Reduced T cell response in carcinogen-sensitive Donryu rats compared with carcinogen-resistant DRH rats

Carcinogen-resistant DRH rats were developed from carcinogen-sensitive Donr yu rats, which showed a high incidence of hepatic tumors when they were exp osed to 3'-methyl-4-dimethyl-aminoazohenzene(3'-MeDAB(4)) or other aminoazo hepatocarcinogens. In order to study the mechanism of the difference of ca rcinogenesis, we studied the immunological competence of Donryu rats compar ed with that of DRH rats. Anti-keyhole limpet hemocyanin (KLH) antibody and KLH-specific delayed hypersensitivity (DTH) responses after immunization w ith KLH were reduced in Donryu rats compared with DRH rats. Proliferative r esponses of spleen cells to KLH and nonspecific mitogens such as conconaval in A (Con A) and phytohemagglutinin (PHA) were significantly lower in Donry u rats than in DRH rats. Upon the cross-linking of T cell receptor (TCR) co mplex using anti-CD3 monoclonal antibody (Mab), spleen cells from Donryu ra ts proliferated poorly, Two other strains of rats, SD and Wistar, exhibited high responsiveness, comparable to that of DRH rats, indicating that the r esponsiveness of Donryu rats was impaired. The production of interleukin-2 (IL-2) upon stimulation with Con A and the responsiveness of Con A blasts t o exogenous IL-2 were also attenuated in Donryu rats. In contrast to T cell responsiveness, natural killer (NK) cell activity of spleen was increased in Donryu rats, Flow cytometric analysis revealed that the expression of CD 4 and CD8 on T cells was decreased in Donryu rats, though the expression of other T cell markers such as CD2, CD3 and CD5 was not different. These res ults indicate that Donryu rats, which have been used in many years for canc er research in Japan, have impaired immunological surveillance mechanisms. This is likely to be one of the factors accounting for the high sensitivity to chemical carcinogens and the high susceptibity to transplanted tumor ce lls of Donryu rats.