Spontaneous Regression in Murine Hypersensitivity Pneumonitis: Lack of Immunological Tolerance

Abstract

We have reported a murine model of hypersensitivity pneumonitis (HP) by transnasal administration of Thermoactinomyces vulgaris (Tv) antigen and shown a potential usefulness in the study of the immunopathogenesis of HP. Since we observed spontaneous regression (SR) of the lung lesions with continuous administration of Tv antigen in our model of HP, attempts were made to study if SR is caused by immunological tolerance. The titers of anti-Tv IgG antibody in serum and bronchoalveolar lavage fluid (BALF) did not show any decrement during the period of SR, at the 6th and 9th weeks after the first administration of the antigen. A delayed-type hypersensitivity reaction, i.e. footpad swelling with Tv antigen, did not change significantly during the SR period. Analysis of BALF cells disclosed that Lyt-2-positive cells, i.e. suppressor/cytotoxic T lymphocytes, did not increase to predominate Lyt-1-positive cells. The lymphocyte proliferation test with Tv antigen showed that the lung lymphocytes reacted to Tv antigen as well as concanavalin A during the period of SR in a similar magnitude as in the development period (3 weeks after the first treatment with the antigen). Treatment with cyclophosphamide before the period of SR resulted in no delay of SR. Finally, the adoptive cell transfer of spleen T cells obtained from mice during the SR period did not manipulate the development of granulomatous pneumonitis in the recipient mice. We concluded that the events causing SR in our murine model of HP may not involve the induction of immunological tolerance in humoral or cellular immunity.