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Role for Nephritogenic T Cells in Lupus Glomerulonephritis: Progression to Renal Failure Is Accompanied by T Cell Activation and Expansion in Regional Lymph Nodes¹

Department of Internal Medicine, Division of Rheumatology and Immunology, Specialized Center of Research on Systemic Lupus Erythematosus, University of Virginia, Charlottesville, VA 22908

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 V 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from National Institutes of Health (Grants K01DK063065 and R01DK069769 (to H.B.), K01AR051391 (to U.S.D.), and R01AR047988 and P50AR045222 (to S.M.F.)), and Novel Research Grant from Lupus Research Institute (to U.S.D.).

² Address correspondence and reprint requests to Dr. Harini Bagavant, Department of Internal Medicine, Division of Rheumatology and Immunology, Box 800412, Health Sciences Center, University of Virginia, Charlottesville, VA 22908. E-mail address: hb5u{at}virginia.edu

³ Abbreviations used in this paper: SLE, systemic lupus erythematosus; GN, glomerulonephritis; LN, lymph node.

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