Reduced T Cell Response in Carcinogen‐sensitive Donryu Rats Compared with Carcinogen‐resistant DRH Rats

• Published in: Cancer science Vol. 90; no. 12; pp. 1277 - 1284
• Main Authors: Mise‐Omata, Setsuko, Sugiura, Tsutomu, Higashi, Ken, Yamashita, Uki
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1999; Japanese Cancer Association; John Wiley & Sons, Inc
• Subjects: Animals; Antibody Formation - drug effects; Antigen-Presenting Cells - immunology; Antigens, Differentiation, T-Lymphocyte - analysis; Biological and medical sciences; Carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens; Carcinogens - toxicity; CD3 antigen; CD4 antigen; CD5 antigen; CD8 antigen; Chemical agents; Cytokines - biosynthesis; Donryu rat; DRH rat; Flow cytometry; Hemocyanins - administration & dosage; Hemocyanins - immunology; Hypersensitivity (delayed); Hypersensitivity, Delayed - immunology; Immunity, Innate; Immunization; Immunological competence; Immunology; Immunosuppressive Agents - toxicity; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - immunology; Lymphocytes; Lymphocytes T; Male; Medical sciences; Methyldimethylaminoazobenzene - toxicity; Mitogens; Monoclonal antibodies; Natural killer cells; NK cell; Rats; Rats, Inbred Strains; Rodents; Spleen; Spleen - cytology; Spleen - immunology; T cell; T cell receptors; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumor cells; Tumors; Immune response; Rat; Liver; Rodentia; Hepatic disease; Cellular immunity; Malignant tumor; Carcinogenesis; Natural killer cell; Carcinogen; Azo compound; Vertebrata; Experimental disease; Mammalia; Sensitivity resistance; Animal; T-Lymphocyte; Tertiary amine; Digestive diseases; Immunocompetence; Lymphocyte; Comparative study
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.1999.tb00709.x

Carcinogen‐resistant DRH rats were developed from carcinogen‐sensitive Donryu rats, which showed a high incidence of hepatic tumors when they were exposed to 3?‐methyl‐4‐dimethyl‐aminoazobenzene (3′‐MeDAB4) or other aminoazo hepatocarcinogens. In order to study the mechanism of the difference of carcinogenesis, we studied the immunological competence of Donryu rats compared with that of DRH rats. Anti‐keyhole limpet hemocyanin (KLH) antibody and KLH‐specific delayed hypersensitivity (DTH) responses after immunization with KLH were reduced in Donryu rats compared with DRH rats. Proliferative responses of spleen cells to KLH and nonspecific mitogens such as conconavalin A (Con A) and phytohemagglutinin (PHA) were significantly lower in Donryu rats than in DRH rats. Upon the cross‐linking of T cell receptor (TCR) complex using anti‐CD3 monoclonal antibody (Mab), spleen cells from Donryu rats proliferated poorly. Two other strains of rats, SD and Wistar, exhibited high responsiveness, comparable to that of DRH rats, indicating that the responsiveness of Donryu rats was impaired. The production of interleukin‐2 (IL‐2) upon stimulation with Con A and the responsiveness of Con A blasts to 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 CD4 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 results indicate that Donryu rats, which have been used in many years for cancer 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 cells of Donryu rats.