Experimental glomerulonephritis is attenuated by CD8+ T cell chimerism and prevented by Mls-1-incompatible thymocytes.
Chronic graft-versus-host disease (GvHD) in mice is a model resembling glomerulonephritis in human systemic lupus erythematosus. In the present study congenic mouse strains were used to investigate the pathogenetic role of (1) donor T cell subset chimerism and (2) donor thymocytes in this model. In GvHD employing minor lymphocyte-stimulating-1 (Mls-1)-compatible donors and recipients, full-blown immune complex glomerulonephritis was associated with a low-donor CD8(+) T cell chimerism. Injection of lymphocytes from Mls-1-negative donors (Mls-1(b)) into Mls-1-positive recipients (Mls-1(a)) induces a type of GvHD characterized by rapid self-limitation accompanied by the immediate inhibition of donor T cell chimerism and the absence of glomerulonephritis. However, omission of thymocytes from the donor inoculate does result in glomerular depositions containing immunoglobulins. These results suggest that donor CD8(+) T cell chimerism is associated with attenuation of immune complex glomerulonephritis, whereas Mls-1-incompatible donor T cell precursors prevent the disease.
Department of Pathology, Leiden University Hospital, Leiden, 2300 RC, The Netherlands. M.Sutmuller@Pathology.Medfac.LeidenUniv.nl
M
M
Sutmuller
H J
HJ
Baelde
O M
OM
Tysma
E
E
de Heer
J A
JA
Bruijn
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002678:Chimera / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007668:Kidney / Q000276:immunology; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016747:Minor Lymphocyte Stimulatory Antigens