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- Title
Expression of the mucosal γδ T cell receptor V region repertoire in patients with IgA nephropathy.
- Authors
Olive, Colleen; Allen, Alice C.; Harper, Steven J.; Wicks, Anthony C. B.; Feehally, John; Falk, Michael C.
- Abstract
IgA nephropathy (IgAN) is characterized by the deposition of IgA in the glomerular mesangium and often leads to progressive renal dysfunction arid kidney failure. We have previously `shown that the mesangial IgA is likely to derive from the bone marrow plasma cells, and suggested that a primary abnormality within the mucosal immune system may underIy the pathogenesis ot IgAN. This study has analyzed the T cell receptor (TCR) variable (V) region expression by γδ T cells in the intestinal mucosa of patients with IgAN. The Vγ and Vδ usage of TCR transcripts was determined using a semiquantitative reverse transcriptase-PCR protocol. Primers specific for the four human Vγ and six Vδ subfamilies were used each with a constant (C) γ or Cδ specific primer and the PCR-amplified TCR transcripts were detected by Southern blotting and oligonucleotide hybridizatio, γ δ TCR V region expression was determined in gut biopsies and peripheral blood of 11 patients with IgAN, and the TCR Vγ and Vδ repertoires were compared to those in gut and peripheral blood of' 11 control individuals. γδ T cells in normal blood predominantly expressed Vγ2 (Vγ9 gene) and Vδ2 gene segments whereas those in normal gut mainly expressed V&gamma2; and Vδ3. In IgAN . patients, Vδ2 was also the predominant Vδ gene utilized by peripheral blood γδ T cells, however, we observed a predominance of Vγ3 and reduced Vγ2 usage by these cells, γδ T cells in the gut of IgAN patients mainly used Vγ3 and Vδl While the γ and δ TCR V region repertoire did not differ significantly between the pheripheral blood of patients and controls there were significant differences in V&gamama; and Vδ repertoire expression was significantly decreased in lgAN and control gut biopsies V&gamma³ gene expression was significantly decreased in IgAN gut compared to control gut (<em>P</em>=0.023). In addition, there was a significant decrease in Vδ3 gene expression in IgAN gut compared to control gut (<em>P</em>0.043). These findings indicate that a subpopulation of γδ T cells, which represent the majority of γδ T cells in normal gut mucosa, are significantly diminished in the gut of patients with lgAN. This suggests that a "hole" in the mucosal yδ T cell repertoire may play a fundamental role in contributing to the pathogenesis of lgAN.
- Subjects
KIDNEY diseases; IMMUNE system; MUCOUS membranes; PATIENTS; T cells; CARCINOGENESIS
- Publication
Kidney International, 1997, Vol 52, Issue 4, p1047
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1997.427