Role of T cells in bronchoalveolar space in the development of interstitial pneumonia induced by superantigen in autoimmune-prone mice

To study the mechanisms underlying the development of interstitial pneumonia in autoimmune disease, we analyzed bronchoalveolar lavage fluid (BALF) in an animal model of interstitial pneumonia in which an intratracheal instillation of staphylococcal enterotoxin B (SEB) induced interstitial pneumonia in autoimmune-prone mice. Increases in the numbers of total cells, macrophages, lymphocytes, and neutrophils were observed in BALF from SEB-treated MRL +/+ mice, and peaked at 3 d after SEB administration (Day 3), Flow cytometric analyses revealed increases in SEB-reactive V beta 8(+) T cells, indicating that SEB-reactive cells play an important role in bronchoalveolar space, The expressions of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, JE/monocyte chemoattractant protein-1, regulated on activation, normal T cells expressed and secreted, and KC/gro messenger RNA (mRNA) in BALF cells from SEB-treated mice peaked at Day 3. Increased expression of TNF-a mRNA was observed mainly in macrophages and CD8(+) T cells, and the increase in IFN-gamma mRNA was observed mainly in CD8(+) T cells in BALF at Day 3, The expression of platelet-derived growth factor mRNA was very weak at Day 3 but strongly expressed at Day 14. An immunosuppressant, FK506, but not corticosteroid, suppressed SEB-induced T-cell expansion in BALF as well as increased cytokine and chemokine production in the bronchoalveolar space of SEB-treated mice. Histologically, FK506 but not corticosteroid significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Further, transfer of T cells of MRL +/+ mice with SEB into SCID mice gave rise to interstitial pneumonia, These results suggest that superantigen-reactive T cells in the bronchoalveolar space may trigger the development of interstitial pneumonia in this model. Fujiki, M., T. Shinbori, M. Suga, H. Miyakawa, and M. Ando. 1999. Role of T cells in bronchoalveolar space in the development of interstitial pneumonia induced by superantigen in autoimmune-prone mice.