Usage of T Cell Receptor Variable Segments of the Beta-Chain in IgA Nephropathy

Abstract

Background: We previously reported that glomerulonephritis associated with Staphylococcus aureus infection (SAGN) showed an increased usage of T cell receptor Vβ 5.3 and 8 in peripheral lymphocytes and mesangial IgA and IgG depositions. To elucidate the immunological mechanisms and pathogenesis of IgA nephropathy, we analyzed the usage of TCR Vβ in both peripheral blood lymphocytes (PBLs) and renal infiltrating T cells from IgA-N patients. Methods: In 38 patients with IgA nephropathy and controls, the usage of TCR Vβ in PBLs were analyzed using monoclonal antibodies against Vβ 3.1, Vβ 5.1, Vβ 5.2 + 5.3, Vβ 5.3, Vβ 6.7, Vβ 8, Vβ 12.1, and Vβ 13.1 + 13.3 with three-color flow cytometry. Furthermore, we examined immunohistochemically renal biopsy specimens using antibodies against Vβ 5.3 and Vβ 8. Results: The percentages of DR+CD4+CD8– cells, CD45RO+CD4+ cells, and CD45RO+CD4+DR+ cells in PBLs from IgA nephropathy were significantly higher than controls. The percentages of TCR Vβ 5.3 positive cells and TCR Vβ 8 positive cells in PBLs from patients were 1.3 ± 0.1 and 3.1 ± 0.2%, and both were significantly higher than controls. The percentage of renal interstitial TCR Vβ 5.3 expression was significantly higher than that in PBLs. However, there was no significant difference between the TCR Vβ 8 expression in the interstitium and that in PBLs. Conclusions: TCR Vβ 5.3 and 8 usage and broad CD4+ T cell activation have occurred in IgA nephropathy. These changes were similar but weak compared with formerly reported SAGN.