Expression of T cell receptor variable region families by bone marrow gammadelta 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. Gammadelta T cells are regulators of mucosal IgA production and oral tolerance. We have described previously a deficiency of gammadelta T cells expressing Vgamma3 and Vdelta3 from the duodenal mucosa in IgAN. Since pIgA production is displaced to the BM, we have now studied BM gammadelta T cells in IgAN. Peripheral blood and BM aspirates were obtained from 14 patients with IgAN and 15 controls. Expression of TCR gamma and delta V region families was analysed by semiquantitative RT-PCR, and CDR3 spectratyping of Vgamma1-4 and Vdelta3 genes was performed. We found no difference between IgAN and controls in the V region usage of blood gammadelta T cells. However, in the BM of patients with IgAN, there was significantly reduced expression of the V region families Vgamma3 and Vdelta3, with the decrease in Vdelta3 being particularly striking. CDR3 spectratyping showed no abnormalities in blood or BM samples. Vgamma3 and Vdelta3 are underexpressed in the duodenum and the BM in IgAN. The combination of imbalanced mucosal and systemic pIgA production with deficient expression of gammadelta T cells using Vgamma3 and Vdelta3 in both sites may imply a role for these gammadelta T cells in the normal regulation of IgA immune responses, and in the complex immunopathogenesis of IgAN.
Buck
K S
KS
Department of Nephrology, Leicester General Hospital, Leicester, UK.
Foster
E M
EM
Watson
D
D
Barratt
J
J
Pawluczyk
I Z A
IZ
Knight
J F
JF
Feehally
J
J
Allen
A C
AC
D000328:Adult; D000368:Aged; D022801:Complementarity Determining Regions / Q000032:analysis; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta