Autoreactive T cells in murine lupus: origins 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 alphabeta T cells. Recent work in murine lupus has confirmed this notion and demonstrated that autoantigen-specific alphabeta T cells are absolutely required for full penetrance of disease, with such autoreactive alphabeta T cells, even in Fas-intact mice, likely arising from defects in peripheral tolerance. These studies have also revealed a network of regulation that also involves nonclassical pathogenic and downregulatory alphabeta and gammadelta T cells, suggesting that the lupus immune system involves more complex interactions than the conventional paradigm suggests.