Bone marrow cell transfer of autoimmune diseases in a MRL strain of mice with a deficit in functional Fas ligand: dissociation of arteritis from glomerulonephritis.
MRL/MpTn-gld/gld (MRL/gld) mice, which are deficient in a functional Fas ligand (FasL), spontaneously develop autoimmune diseases involving both lethal glomerulonephritis and systemic arteritis, while MRL/Mp-+/+ (MRL/+) and C3H/HeJ-gld/gld (C3H/gld) do not. To determine the cells responsible for the development of glomerulonephritis and arteritis, we transferred bone marrow cells from MRL/gld mice to undiseased MHC-compatible gld/gld or +/+ mice. In bone marrow irradiation chimeras, MRL/gld bone marrow cells were transferred to lethally irradiated MRL/+ or C3H/HeJ-+/+ (C3H/+) mice, and both recipients developed glomerulonephritis associated with hypergammaglobulinemia without causing graft-versus-host (GVH)-like diseases. However, a striking difference between them was that MRL/+ recipients developed arteritis, but C3H/+ recipients did not. In bone marrow mixed chimeras formed by transferring MRL/gld bone marrow cells to unirradiated mice, the MRL/gld bone marrow cells induced glomerulonephritis in C3H/gld mice, but not in C3H/+ and MRL/+ mice. These results indicate that bone marrow cells from MRL/gld mice can cause glomerulonephritis in mice, even in those with a C3H background, possibly if they survive longer by escaping from Fas-mediated apoptosis, while the development of arteritis requires the MRL genetic background in the recipients. This is the first report of the transfer of arteritis in lupus mice to undiseased recipients.
Ito
Mitsuko R
MR
Department of Pathology, Ehime University of School of Medicine, Sitsukawa, Japan. mitsukoi@m.ehime-u.ac.jp
Ono
Masao
M
Itoh
Junpei
J
Nose
Masato
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D017209:Apoptosis; D001167:Arteritis / Q000209:etiology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology; D001853:Bone Marrow / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D004247:DNA / Q000276:immunology; D053222:Fas Ligand Protein; D005921:Glomerulonephritis / Q000209:etiology* / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008815:Mice, Inbred Strains; D011828:Radiation Chimera; D013045:Species Specificity
D000974:Antibodies, Antinuclear; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D004247:DNA