| First Author | Chowdhary VR | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 4 | Pages | 2054-62 |
| PubMed ID | 22798666 | Mgi Jnum | J:189749 |
| Mgi Id | MGI:5446955 | Doi | 10.4049/jimmunol.1201097 |
| Citation | Chowdhary VR, et al. (2012) Chronic exposure to staphylococcal superantigen elicits a systemic inflammatory disease mimicking lupus. J Immunol 189(4):2054-62 |
| abstractText | Chronic nasal and skin colonization with superantigen (SAg)-producing Staphylococcus aureus is well documented in humans. Given that trans-mucosal and trans-cutaneous absorption of SAgs can occur, we determined whether chronic exposure to small amounts of SAg per se could activate autoreactive CD4(+) and CD8(+) T cells and precipitate any autoimmune disease without further external autoantigenic stimulation. Because HLA class II molecules present SAg more efficiently than do mouse MHC class II molecules, HLA-DQ8 transgenic mice were implanted s.c. with mini-osmotic pumps capable of continuously delivering the SAg, staphylococcal enterotoxin B (total of 10 mug/mouse), or PBS over 4 wk. Chronic exposure to staphylococcal enterotoxin B resulted in a multisystem autoimmune inflammatory disease with features similar to systemic lupus erythematosus. The disease was characterized by mononuclear cell infiltration of lungs, liver, and kidneys, accompanied by the production of anti-nuclear Abs and deposition of immune complexes in the renal glomeruli. The inflammatory infiltrates in various organs predominantly consisted of CD4(+) T cells bearing TCR Vbeta8. The extent of immunopathology was markedly reduced in mice lacking CD4(+) T cells and CD28, indicating that the disease is CD4(+) T cell mediated and CD28 dependent. The absence of disease in STAT4-deficient, as well as IFN-gamma-deficient, HLA-DQ8 mice suggested the pathogenic role of Th1-type cytokines, IL-12 and IFN-gamma. In conclusion, our study suggests that chronic exposure to extremely small amounts of bacterial SAg could be an etiological factor for systemic lupus erythematosus. |
