MHC class I pathway is not required for the development of crescentic glomerulonephritis in mice.
MHC II and CD4+ T cells are required for anti-glomerular basement membrane (GBM) globulin-initiated crescentic glomerulonephritis (GN) in mice, but the role of MHC I and CD8+ T cells is unclear. The cytolytic function of CD8+ T cells requires recognition of peptide antigens presented on MHC I. CD8+ T cells can also perform helper functions via cytokine production. The contribution of MHC I to crescentic GN was investigated using TAP-1 gene knock out (TAP-1-/-) mice, which have deficient MHC I antigen presentation. Heterozygous TAP-1 mice have normal MHC I expression and developed GN with crescents in 42 +/- 4% of glomeruli (normal 0%), proteinuria (9.1 +/- 1.6 mg/20 h, normal 1.5 +/- 0.3 mg/20 h) and impaired renal function (creatinine clearance 110 +/- 8 microl/min, normal 193 +/- 10 microl/min) following administration of sheep anti-mouse GBM globulin. TAP-1-/- mice, which have extremely low MHC I expression and reduced CD8+ T cells, developed similar GN with 39 +/- 3% crescents, proteinuria (12.7 +/- 4.3 mg/20 h) and impaired renal function (creatinine clearance 123 +/- 20 microl/min). In vivo antibody-induced CD8 depletion did not attenuate crescent formation or protect renal function in C57Bl/6 mice developing GN, although significant reduction in proteinuria (5.3 +/- 1.2 mg/20 h, P = 0. 012) and glomerular recruitment of CD4+ T cells and macrophages were observed compared with control treated mice with GN. These data demonstrate that MHC I is not required for development of crescentic GN in mice. The MHC I-independent contribution of CD8+ T cells to proteinuria and inflammatory cell recruitment suggests that they may serve a 'helper' rather than cytolytic role in this disease.
Li
S
S
The Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Holdsworth
S R
SR
Tipping
P G
PG
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005916:Globulins / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008212:Lymphocyte Depletion; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012756:Sheep
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D005916:Globulins; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse