T cell receptor beta chain (TCR-Vβ) repertoire of circulating CD4⁺CD25^−, CD4⁺CD25^lowand CD4⁺CD25^highT cells in patients with long-term renal allograft survival

Abstract

Summary The mechanisms underlying maintenance of renal allografts in humans under minimal or conventional immunosuppression are poorly understood. There is evidence that CD4+ CD25+ regulatory T cells and clonal deletion, among other mechanisms of tolerance, could play a key role in clinical allograft survival. Twenty‐four TCR‐Vβ families were assessed in CD4+ CD25−, CD4+ CD25low and CD4+ CD25high T cells from patients with long‐term renal allograft survival (LTS), patients exhibiting chronic rejection (ChrRx), patients on dialysis (Dial) and healthy controls (HC) by flow cytometry. LTS patients presented a higher variability in their TCR‐Vβ repertoire, such decreased percentage of Vβ2+, Vβ8a+ and Vβ13+ in CD4+ CD25low and high compared with CD4+ CD25− subset and increased Vβ4 and Vβ7 families in CD4+ CD25high T cells exclusively. Additionally, LTS patients, particularly those that were not receiving calcineurin inhibitors (CNI), had increased percentages of CD4+ CD25high T cells when compared with Dial (P < 0.05) and ChrRx (P < 0.05) patients. Our results suggest that a differential expression of particular TCR‐Vβ families and high levels of circulating CD4+ CD25high T cells in long‐term surviving renal transplant patients could contribute to an active and specific state of immunologic suppression. However, the increase in this T cell subset with regulatory phenotype can be affected by CNI.

Composition and diversity analysis of the B‑cell receptor immunoglobulin heavy chain complementarity‑determining region 3 repertoire in patients with acute rejection after kidney transplantation using high‑throughput sequencing

“…Concerning the particular cell types involved, several studies have discussed the role of T-cell receptors (TCRs) in transplant rejection. Velásquez et al (8) suggested that differential expression of particular TCR β chain variable families and high levels of circulating CD4(+) CD25 (high) T cells in long-term surviving renal transplant patients contribute to an active and specific state of immunologic suppression. Matsutani et al (9) indicated that the skew in TCR usage was correlated with the levels of clonal T-cell expansion, indicating that the expanding T cells were responsible for the skew in TCR usage.…”