Alleviation of renal disease and lymphadenopathy in MRL-Fasp(lrcg)/Fas(lprcg) (MR-lpr(cg)) mice neonatally infected with mouse mammary tumor virus encoding superantigen strongly reactive with TCR Vbeta8.2 element.
Mouse mammary tumor virus transmitted by FM mice (FM-MMTV) encodes a superantigen (SAg) characterized by strong reactivity with TCR Vbeta8.2 element and broad spectrum of Vbeta reactivity. To investigate what effects the expression in vivo of FM-MMTV SAg exhibits on the course of the disease in a lupus-prone model, MRL/MpJ-Fas(lprcg)/Fas(lprcg) (MRL-lpr9cg) mice, neonatally FM-MMTV-infected MRL-lprcg(MMTV) and uninfected MRL-lpr(cg) mice were compared for various disease parameters. In MRL-lprcg(MMTV), survival was significantly prolonged, glomerulonephritis, proteinuria, and lymphadenopathy were clearly ameliorated, and the production of serum immunoglobulin G (IgG), complement-activating IgG2a, and cryogenic IgG3 autoantibodies, which are thought to be pathogenic to kidneys, and circulating immune complexes (IC), and glomerular IC deposition were significantly suppressed. FM-MMTV infection deleted Vbeta8.2+ cells by about 90% and Vbeta14+ cells less efficiently in all of the CD4+, CD8+, and B220+ CD4- CD8- or double-negative (DN) T-cell populations, and Vbeta8.1+ cells in the CD4+ population but not in the others. Similar deletion profiles of CD8+ and DN T cells support that DN T cells are derived from the CD8 lineage. The results imply that the specific regulation of the immune system with viral SAg has a potential for development of an attractive immunomodulatory therapy of autoimmune diseases.
Matsuzawa
A
A
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Japan. atmatsu@oregano.ocn.ne.jp
Yasuda
T
T
Zhang
Y
Y
Nagase
H
H
Yoshimoto
T
T
Kimura
M
M
Tsubura
A
A
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000097:blood; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy; D008181:Lupus Nephritis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D008206:Lymphatic Diseases / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D008221:Lymphoid Tissue / Q000473:pathology; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000276:immunology*; D011507:Proteinuria; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology / Q000821:virology; D018089:Superantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D019014:fas Receptor / Q000235:genetics
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D007136:Immunoglobulins; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C109168:T-cell receptor Vbeta 8.2; D019014:fas Receptor