Autoreactive T cells in murine lupusOrigins and Roles in Autoantibody Production

The conventional paradigm to explain systemic lupus erythematosus (SLE) is that disease results from tissue deposition of pathogenic autoantibodies and immune complexes, secondary to activation of autoreactive B cells in the context of help from αΒ T cells. Recent work in murine lupus has confirmed this notion and demonstrated that autoantigen-specific αΒ T cells are absolutely required for full penetrance of disease, with such autoreactive αΒ T cells, even in Fasintact mice, likely arising from defects in peripheral tolerance. These studies have also revealed a network of regulation that also involves nonclassical pathogenic and downregulatory αΒ and γδ T cells, suggesting that the lupus immune system involves more complex interactions than the conventional paradigm suggests.