Self-limiting systemic autoimmune disease during reconstitution of T cell-deficient mice with syngeneic T cells: support for a multifaceted role of Tcells in the maintenance of peripheral B cell tolerance

The T cell compartment can be partially reconstituted in mice with targeted inactivation of the TCR C-beta and C-delta genes by injection of mature, s yngeneic T cells. Surprisingly, during this reconstitution high titers of I gG anti-nuclear antibodies and symptoms of systemic autoimmune disease deve lop. However, this autoimmune response is transient and aged, reconstituted mice show no overt signs of disease. The autoantibody response appears to be derived from a pre-existing population of host self-reactive B cells and requires CD40 ligand-mediated co-stimulation from donor cells. Diminution of this response is coincident with a vigorous germinal center reaction and the disappearance of a subpopulation of activated B cells that expresses e levated levels of Fas. Collectively, our data support the idea that T cells play a multifaceted role in the maintenance of peripheral B cell tolerance that includes mediating the activation-induced death of autospecific B cel ls.