Strain variation in BCG-induced chronic pulmonary inflammation in mice: control by a cyclophosphamide-sensitive thymus-derived suppressor cell.
We previously reported that only certain strains of inbred mice develop intense chronic granulomatous inflammation (CGI) in the lungs and spleen in response to an i.v. injection of killed BCG in an oil-in-saline emulsion (BCG-E). The capacity to respond did not appear to be controlled by genes within the H-2 complex; subsequent studies have shown that genes linked to the Igh allotype complex influence the development of CGI. In other systems, unresponsiveness to certain antigens has been shown to be because of cyclophosphamide- (Cy) sensitive suppressor cells. We therefore used Cy as a probe to study mechanisms of unresponsiveness in low-responder (LR) CBA mice. The results indicate that LR mice could be converted into high responders (HR) by treatment with 100 mg of Cy per kilogram of body weight 2 days before injection with BCG-E. In addition, the effects of Cy were inhibited by the provision of syngeneic whole or purified spleen T cells from mice injected 7 days previously with BCG-E. Cells responsible for abolition of the Cy effect were sensitive to anti-Thy-1 serum + C. Thus, the intensity of BCG-E-induced CGI in mouse lungs is controlled by a population of Cy-sensitive T lymphocytes.
D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology*; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D007519:Isoantigens; D007700:Kinetics; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000150:complications / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013163:Splenomegaly / Q000209:etiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D001500:BCG Vaccine; D007519:Isoantigens; D003520:Cyclophosphamide