Predominance of T cell receptor Vδ3 in small bowel biopsies from celiac disease patients

Abstract

SUMMARYIncreased numbers of T cells bearing the 7^ antigen receptor {•^8 T cells) have been reported in small bowel biopsies of patients with latent, active or treated coeliac disease. We have studied jejunal biopsies from seven children with coeliac disease and 10 children with normal gut histology to characterize 7* T cell receptor (TCR) variable region gene subfamily expression in resident 7* T cells and compared the results with the findings in peripheral blood mononuclear cells (PBMC) obtained on the same day as the gut biopsy. Molecular analysis of RNA extracted from PBMC and biopsies was performed by reverse transcription and amplification with the polymerase chain reaction using primers specific for six TCR V5 families and four TCR V7 families. We report, first, that a significantly increased number of 7* T cells expressing the TCR V53 subfamily {P = 0008) was observed in jejunal biopsies from children with coeliac disease, and second, that 75 T cell V region subfamily populations in gut differed from those seen in PBMC for both control and coeliac patients. Significantly reduced numbers of TCR V62, V(53, V65 {P < 0 01) and V72, V7^4 {P < 0 01) T cells were found in gut compared with PBMC. The difference in 7^ T cell repertoire observed between gut and blood may reflect differences in the nature of the antigens usually encountered in these two compartments. The over-representation of TCR V(53 in patients with coeliac disease suggests a specific role for these cells in the induction or maintenance of the jejunal abnormality associated with this disease.

Single-cell TCR sequencing of gut intraepithelial γδ T cells reveals a vast and diverse repertoire in celiac disease

“…Studies of the small-intestinal γδ T cell repertoire are scarce [14][15][16] , and even more so in the context of CeD 17,18 . A study by Han et al showed that activated gut-homing γδ T cells and CD8 + αβ T cells increase in the blood of CeD patients on day 6 after gluten challenge, along with gluten-specific CD4 + T cells.…”

Persistent Changes in Circulating and Intestinal γδ T Cell Subsets, Invariant Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Children and Adults with Coeliac Disease

“…Within the peripheral blood, the majority of γδ T cells possess an invariant Vγ9Vδ2 T cell receptor, whereas the Vδ1/Jδ1-encoded chain predominates in healthy gut tissue [9]. The Vδ1 subset is reportedly expanded in the intestinal epithelium in CD [10–14] and expresses NKG2A and TGF-β, suggesting an immunoregulatory role [8], but data regarding other γδ subsets in the intestine is lacking, or contradictory [15–17]. Since murine γδ T cell subsets differ distinctly from human, and the majority of work on γδ T cells in humans involves the Vδ2 subset, clarification and distinction of the roles discrete γδ subsets play is important, particularly if these cells are to be successfully exploited for immunotherapy [18,19].…”

Molecular, Cellular and Functional Analysis of TRγ Chain along the European Sea Bass Dicentrarchus labrax Development

“…Additional research needs to be performed to clarify the biological significance of transcript down-regulation and/or the redistribution of γδ T cells. In fact, the lack of enhancement of immune functions does not necessarily translate to decreased health, e.g., over-activated γδ T cells may enhance the pathology associated with inflammatory bowel [ 71 ] or celiac disease in humans [ 72 ].…”