Disruption of T cell tolerance to self-immunoglobulin causes polyclonal B cell stimulation followed by inactivation of responding autoreactive T cells

Scavenger receptor (SR)-specific delivery by maleylation of a ubiquitous se lf-protein, Ig, to SR-bearing APCs results in self-limiting induction of au toimmune effects in vivo. Immunization with maleyl-Ig breaks T cell toleran ce to self-Ig and causes hypergammaglobulinemia, with increases in spleen w eight and cellularity. The majority of splenic B cells show an activated ph enotype upon maleyl-Ig immunization, leading to large-scale conversion to a CD138(+) phenotype and to significant increases in CD138-expressing spleni c plasma cells. The polyclonal B cell activation, hypergammaglobulinemia, a nd autoreactive Ig-specific T cell responses decline over a 2-mo period pos timmunization. Following adoptive transfer, T cells from maleyl-Ig-immune m ice taken at 2 wk postimmunization can induce hypergammaglobulinemia in the recipients, but those taken at 10 wk postimmunization cannot. Hypergammagl obulinemia in the adoptive transfer recipients is also transient and is fol lowed by an inability to respond to fresh maleyl-Ig immunization, suggestin g that the autoreactive Ig-specific T cells are inactivated peripherally fo llowing disruption of tolerance. Thus, although autoreactive T cell respons es to a ubiquitous self-Ag, Ig, are induced by SR-mediated delivery to prof essional APCs in vivo resulting in autoimmune pathophysiological effects, t hey are effectively and rapidly turned off by inactivation of these activat ed Ig-specific T cells in vivo.