Interferon alpha causes SLE by expanding CD4- CD8- double negative T cell

Objective: It has been hypothesized that high interferon alpha (IFNα) levels cause systemic lupus erythematosus (SLE), however, the direct proof for this is lacking. We have shown that sole increase of interferon alpha (IFNα) in doxycycline (Dox)-inducible transgenic (IFNα Tg) mice induces production of anti-dsDNA antibody and renal disease akin to human SLE. In this study, we have investigated how IFNα functions and to what extent IFNα operates in the pathogenesis of SLE. Methods: We made C57BL6/FVBN TetOp-mIFNα/EμSR-tTA transgenic female mice in which IFNα was expressed after the cessation of Dox. We transferred CD4+ (5x106), CD8+ (5x106) and CD4- CD8- double negative (DN) T (3x105) subsets derived from 30 weeks Dox-off IFNα Tg mice into naive recipient mice twice. In additional experiment, CD4+ (8x106), CD8+ (8x106) and DN T (9x105) subsets were transferred. Anti-dsDNA antibody, serum IC, proteinuria and renal lesion of recipient mice were evaluated. Results: Transfer of DN T (3x105) subset of Dox-off IFNα Tg mice induced IC-mediated mesangio-proliferative glomerulonephritis. However, there were no increases in anti-dsDNA antibody, serum IC nor proteinuria after the transfer of DN T (9x105) subset. It was, however, noted that alopecia, was developed by transfer of DN T (9x105) subset. Conclusion: DN T cell is responsible for the induction of lupus glomerulonephritis and alopecia.