Role for nephritogenic T cells in lupus glomerulonephritis: progression to renal failure is accompanied by T cell activation and expansion in regional lymph nodes.
Autoreactive T cells are critical in the initiation and maintenance of autoantibody responses that are a hallmark of systemic lupus erythematosus. However, the direct contribution of T cells in end-organ disease like lupus glomerulonephritis (GN) is poorly understood. In this study, we investigated the role of T cells in progression of lupus GN in NZM2328 mice, a murine model of spontaneous systemic lupus erythematosus. At 26 wk of age, NZM2328 female mice showed glomerular immune complex deposits and acute proliferative GN. This was associated with up-regulation of MHC class II and the detection of T cells and CD11c(+) dendritic cells in the glomeruli. The regional lymph nodes (LN) showed preferential activation of T cells and an oligoclonal T cell response with skewed expansion of certain Vbeta families. This suggests an Ag-driven response occurring in the regional LN of nephritic mice during acute GN. In contrast, male NZM2328 mice developed glomerular immune complexes and acute GN, but rarely progressed to fatal chronic GN. Significantly, male kidneys at 40 wk of age did not have detectable dendritic cells and T cells in the glomeruli. Thus, glomerular immune complex deposition initiates an immune response against renal Ags in the regional LN, leading to T cell recruitment into the kidney during acute proliferative GN. This T cell activation and infiltration are influenced by gender-dependent end-organ factors and may determine the progression of acute GN to chronic GN and renal failure.
Bagavant
Harini
H
Department of Internal Medicine, Division of Rheumatology and Immunology, Specialized Center of Research on Systemic Lupus Erythematosus, University of Virginia, Charlottesville, VA 22908, USA. hb5u@virginia.edu
Deshmukh
Umesh S
US
Wang
Hongyang
H
Ly
Timothy
T
Fu
Shu Man
SM
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000949:Histocompatibility Antigens Class II; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D051437:Renal Insufficiency / Q000209:etiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology*
D000936:Antigen-Antibody Complex; D000949:Histocompatibility Antigens Class II