Establishment of Germfree Athymic Nude Rats and T Cell Requirement for BCG-Induced Polyarthritis and Granuloma Formation

Abstract

We established and maintained germfree (GF) athymic nude rats (rnu/rnu) raised from specific pathogen free (SPF) nude rats, since 1981 in the Animal Center of Tokai University. None of the GF nude rats developed polyarthritis until they were reconstituted with spleen cells from normal adult euthymic GF rnu/ + rats. All of the spleen cell reconstituted-GF nude rats developed severe polyarthritis comparable to that seen in the SPF and GF euthymic rnu/ + rats, in terms of the day of onset, severity and incidence and histopathology. Epithelioid granuloma in the regional lymph nodes of the GF nude rats was immature and smaller than that of SPF nude rats. The spleen cell-reconstituted GF nude rats had a large and mature epithelioid granuloma with large central necrosis infiltrated by numerous polymorphonuclear leukocytes and comparable to findings in the SPF and GF rnu/ + rats but larger than in the spleen cell-reconstituted SPF nude rats. We conclude that (1) thymus or T cell functions play a primary role in the development of the disease and the mature epithelioid granuloma formation with a large central necrosis and (2) microbial flora plays a secondary role as an environmental factor in modulating the disease and in the epithelioid granuloma formation, through undetermined mechanisms.