title: The role of host (endogenous) T cells in chronic graft-versus-host autoimmune disease.
abstract: Chronic graft-vs-host (cGVH) disease induced by the transfer of Ia-incompatible spleen cells from one normal mouse strain (such as B6.C-H2(bm12)/KhEg (bm12)) to another (such as C57BL/6) causes an autoimmune syndrome resembling systemic lupus erythematosus (SLE). The role of host-derived T cells in this response is not obvious. Previous reports suggested that host T cells might serve to down-regulate the autoimmune syndrome. To address this issue more definitively, we used CD4 knockout (KO) or CD8KO C57BL/6 (B6) mice as recipients in the bm12-->C57B6 cGVH model. CD4KO B6 mice injected with allogeneic bm12 spleen cells (bm12-->CD4KO group) showed no evidence of cGVH disease. They made no detectable autoantibodies, including anti-chromatin, anti-dsDNA, anti-ssDNA, and rheumatoid factor. They survived at least 20 wks after induction of cGVH disease; and they did not develop nephritis, based on the absence of detectable levels of proteinuria and normal renal histology at the time of sacrifice. By contrast, CD8KO B6 mice (bm12-->CD8KO group) and normal B6 mice (bm12-->B6 group) injected with bm12 spleen cells generally showed similar levels of mortality, nephritis, and autoantibodies, although the autoantibody titers declined somewhat after week 8 in the bm12-->CD8KO group. Control groups of recipients injected with B6 spleen cells showed no induction of autoantibodies. A surprising finding, however, was that the B6-->CD8KO group developed severe histologic glomerulonephritis in the absence of autoantibodies and with decreased immune deposits. These results indicate that endogenous (host) CD4+ T cells play an essential role in the cGVH autoimmune syndrome.
authors.affiliation: Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104-4283, USA.
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: M A
authors.initials: MA
authors.lastname: Maldonado
authors.forename: M
authors.initials: M
authors.lastname: Madaio
authors.forename: R A
authors.initials: RA
authors.lastname: Eisenberg
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology; D016827:CD8 Antigens / Q000235:genetics / Q000502:physiology; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009393:Nephritis / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology
chemical_list: D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens