Expression of T cell receptor variable region families by bone marrow γδ T cells in patients with Iga nephropathy
IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA (pIgA). Abnormalities of the IgA system include reduced mucosal and increased bone marrow (BM) pIgA production. γδ T cells are regulators of mucosal IgA production and oral tolerance. We have described previously a deficiency of γδT cells expressing Vγ3 and Vδ3 from the duodenal mucosa in IgAN. Since pIgA production is displaced to the BM, we have now studied BM γδ T cells in IgAN. Peripheral blood and BM aspirates were obtained from 14 patients with IgAN and 15 controls. Expression of TCR γ and δ V region families was analysed by semiquantitative RT-PCR, and CDR3 spectratyping of Vγ1-4 and Vδ3 genes was performed. We found no difference between IgAN and controls in the V region usage of blood γδ T cells. However, in the BM of patients with IgAN, there was significantly reduced expression of the V region families Vγ3 and Vδ3, with the decrease in Vδ3 being particularly striking. CDR3 spectratyping showed no abnormalities in blood or BM samples. Vγ3 and Vδ3 are underexpressed in the duodenum and the BM in IgAN. The combination of imbalanced mucosal and systemic pIgA production with deficient expression of γδ T cells using Vγ3 and Vδ3 in both sites may imply a role for these γδ T cells in the normal regulation of IgA immune responses, and in the complex immunopathogenesis of IgAN.