Together, these data suggest model-dependent effects of STAT4 in various autoimmune diseases and foreign Ag–driven responses in which STAT4 contributes to T cell–mediated autoimmunity, but it is largely dispensable for AFC, GC, and Th cell responses in B cell–mediated autoimmunity, including SLE and certain foreign Ag–driven responses. Here, STAT4 is linked to autoimmune disease.