T lymphocyte-dependent evolution of bacterial cell wall-induced hepatic granulomas.
Injection of streptococcal cell walls (SCW) i.p. into susceptible rats results in dissemination of SCW primarily to the liver, spleen, bone marrow, and peripheral joints. Within the liver, the SCW are phagocytized by the Kupffer cells, initiating a sequence of events leading to the formation of hepatic granulomas. The granulomas are characterized by large numbers of W3/13+, W3/25+ T lymphocytes and Ia+, esterase-positive macrophages. The generation of inflammatory mediators by these mononuclear cells appears to be central to the evolution of the granulomas and the subsequent fibrotic sequelae evoked by the SCW. In the absence of functional T lymphocytes (athymic rats), injection of SCW does not trigger lymphokine production, and organized granulomas do not develop in the livers. Furthermore, inhibition of T lymphocyte proliferation and lymphokine synthesis pharmacologically by cyclosporin A administration in euthymic animals inhibits SCW-induced hepatic granuloma development. Although macrophage function is apparently not impaired as evidenced by IL 1 and PGE2 production, a chronic inflammatory response to SCW cannot be sustained in the absence of T lymphocyte participation. These studies provide insight into the cellular and molecular mechanisms leading to formation and maintenance of chronic granulomatous lesions.
D000818:Animals; D002473:Cell Wall / Q000276:immunology; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D015232:Dinoprostone; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis; D008854:Microscopy, Electron; D015846:Monokines; D011458:Prostaglandins E / Q000096:biosynthesis; D014176:Protein Biosynthesis; D051381:Rats; D011923:Rats, Nude; D013291:Streptococcus / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D007377:Interleukin-3; D008222:Lymphokines; D015846:Monokines; D011458:Prostaglandins E; D015232:Dinoprostone