Self-limiting systemic autoimmune disease during reconstitution of T cell-deficient mice with syngeneic T cells: support for a multifaceted role of T cells 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, syngeneic T cells. Surprisingly, during this reconstitution high titers of IgG anti-nuclear antibodies and symptoms of systemic autoimmune disease develop. 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 elevated 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 cells.
Lentz
V M
VM
Department of Microbiology and Immunology, Jefferson Medical College, BLSB 708, 233 South 10th Street, Philadelphia, PA 19107, USA.
Manser
T
T
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D019676:Genes, T-Cell Receptor delta / Q000235:genetics; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000235:genetics; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics; D017634:Self Tolerance / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta