Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus1

• Published in: The Journal of immunology (1950) 2012-07, Vol.189 (4), p.2054-2062
• Main Authors: Chowdhary, Vaidehi R., Tilahun, Ashenafi Y., Clark, Chad R., Grande, Joseph P., Rajagopalan, Govindarajan
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1201097

Chronic nasal and skin colonization with superantigen (SAg) 2 -producing Staphylococcus aureus is well documented in humans. Given that trans-mucosal and trans-cutaneous absorption of SAg 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. Since human leukocyte antigen (HLA) class II molecules present SAg more efficiently than mouse MHC class II molecules, HLA-DQ8 transgenic mice were subcutaneously implanted with miniosmotic pumps capable of continuously delivering the SAg, staphylococcal enterotoxin B (SEB, total of 10 μg/mouse) or phosphate buffered saline (PBS), over 4 weeks. Chronic exposure to SEB resulted in a multisystem autoimmune inflammatory disease with features similar to systemic lupus erythematosus (SLE). The disease was characterized by mononuclear cell infiltration of lungs, livers and kidneys, accompanied by the production of antinuclear antibodies and deposition of immune complexes in the renal glomeruli. The inflammatory infiltrates in various organs predominately consisted of CD4 + T cells bearing TCR Vβ8. The extent of immunopathology was markedly reduced in mice lacking CD4 + T cells and CD28, indicating the disease is CD4 + T cell mediated and CD28 dependent. The absence of disease in STAT4-deficient as well as IFN-γ-deficient HLA-DQ8 mice suggested the pathogenic role of Th1-type cytokines, IL-12 and IFN-γ. In conclusion, our study suggests that chronic exposure to extremely small amounts of bacterial SAg could be an etiological factor for SLE.