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 self-protein, Ig, to SR-bearing APCs results in self-limiting induction of autoimmune effects in vivo. Immunization with maleyl-Ig breaks T cell tolerance to self-Ig and causes hypergammaglobulinemia, with increases in spleen weight and cellularity. The majority of splenic B cells show an activated phenotype upon maleyl-Ig immunization, leading to large-scale conversion to a CD138+ phenotype and to significant increases in CD138-expressing splenic plasma cells. The polyclonal B cell activation, hypergammaglobulinemia, and autoreactive Ig-specific T cell responses decline over a 2-mo period postimmunization. Following adoptive transfer, T cells from maleyl-Ig-immune mice taken at 2 wk postimmunization can induce hypergammaglobulinemia in the recipients, but those taken at 10 wk postimmunization cannot. Hypergammaglobulinemia in the adoptive transfer recipients is also transient and is followed by an inability to respond to fresh maleyl-Ig immunization, suggesting that the autoreactive Ig-specific T cells are inactivated peripherally following disruption of tolerance. Thus, although autoreactive T cell responses to a ubiquitous self-Ag, Ig, are induced by SR-mediated delivery to professional APCs in vivo resulting in autoimmune pathophysiological effects, they are effectively and rapidly turned off by inactivation of these activated Ig-specific T cells in vivo.
Choudhury
A
A
National Institute of Immunology, New Delhi, India.
Mukherjee
P
P
Basu
S K
SK
George
A
A
Rath
S
S
Bal
V
V
D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D006942:Hypergammaglobulinemia / Q000276:immunology; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000008:administration & dosage* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000276:immunology*; D008299:Maleic Anhydrides / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D007136:Immunoglobulins; D008299:Maleic Anhydrides; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B