Bacterial Cell Wall-induced Immunosuppression

Asingle intraperitoneal injection of bacterial cell walls derived from groupA streptococci (SCW)' into susceptible rats results in the development of acute and chronic erosive polyarthritis (1, 2) . The pathology of the lesion leading to joint destruction has been shown to be aT cell-dependent, cell-mediated response to the deposition of the group A streptococcal peptidoglycan-polysaccharide polymers in the synovium (3-5). Furthermore, these chronic joint lesions share many common histopathologic, radiologic, and clinical features with human rheumatoid arthritis (6). Another apparent shared feature in patients with rheumatoid arthritis and rodents with SCW-induced arthritis is impaired immunoregulation and suppression of the immune system . Patients with arthritis frequently exhibit suppressed lymphoid cell functions (6-10), and depressed lymphoid cell activity has also been reported in SCW treated rats (2, 11, 12). The mechanism of aberrant immune responsiveness associated with these chronic inflammatory lesions is unknown, although adherent cells have been implicated (2, 10) and deficient IL-2 production has also been reported (11) . Because of the potential importance of impaired immunoregulation in the evolution of chronic inflammatory lesions such as arthritis, we have used the experimental model of SCW-induced chronic inflammation to explore the cellular and molecular pathways of suppressed immune responsiveness . In this study, we document a role for the adherent macrophage population in mediating the suppressed lymphoproliferative responses characteristic of the spleens of SCW-treated Lewis (LEW) rats . Furthermore, this suppression is mediated by a soluble suppressor factor released by SCW-activated macrophages within the spleen . Subsequent studies to characterize this suppressor activity revealed it to be consistent with the polypeptide, transforming growth factor R (TGRR).