Analysis of T cell receptor Vβ diversity in peripheral CD4+ and CD8+ T lymphocytes in patients with autoimmune thyroid diseases

Abstract

Summary Autoimmune thyroid diseases are characterized by intrathyroidal infiltration of CD4+ and CD8 + T lymphocytes reactive to self-thyroid antigens. Early studies analysing T cell receptor (TCR) Va gene usage have shown oligoclonal expansion of intrathyroidal T lymphocytes but not peripheral blood T cells. However, TCR Vb diversity of the isolated CD4 + and CD8 + T cell compartments in the peripheral blood has not been characterized fully in these patients. We performed complementarity-determining region 3 (CDR3) spectratyping as well as flow cytometric analysis for the TCR Vb repertoire in peripheral CD4+ and CD8 + T cells from 13 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis. Polyclonal TCR Vb repertoire was demonstrated by flow cytometry in both diseases. In contrast, CDR3 spectratyping showed significantly higher skewing of TCR Vb in peripheral CD8 + T cells but not CD4+ T cells among patients with Hashimoto's thyroiditis compared with healthy adults. We found trends towards a more skewed CDR3 size distribution in those patients having disease longer than 5 years and requiring thyroid hormone replacement. Patients with Graves' disease exhibited no skewing both in CD4 + and CD8 + T cells. These findings indicate that clonal expansion of CD8 + T cells in Hashimoto's thyroiditis can be detected in peripheral blood and may support the role of CD8+ T cells in cell-mediated autoimmune attacks on the thyroid gland in Hashimoto's thyroiditis.

High-Throughput Analysis of the T Cell Receptor Beta Chain Repertoire in PBMCs from Chronic Hepatitis B Patients with HBeAg Seroconversion

“…Molecular structural analysis has revealed that CDR3 mainly recognizes MHC molecules bound to antigenic peptides [20, 21]. Hence, analysis of CDR3 can reveal changes in antigen-stimulated T cells [22, 23], the number of T cell clones, and T cell functioning [24, 25]. …”

Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection

“…CDR3 primarily recognizes antigen-derived peptides bound to a MHC molecule, an interaction that has been observed through crystal structure analysis. 19,20 Therefore, the analysis of a CDR3 profile can reveal changes in the T-cell population stimulated by a specific antigen, 21,22 the amount of a particular T-cell clone and the functional status of T cells. 23,24 T lymphocytes are primarily divided into the CD4 1 and CD8 1 subsets.…”

Analysis of T cell receptor V beta diversity in peripheral CD8(+) T lymphocytes in patients with hepatitis B infection

“…The region that shows most variability is the so called "complementary-determining region 3" (CDR3). The TCR Vbeta repertoire in CDR3 can reflect a diverse TCR repertoire [4]. Thus, the analysis and detection of the clonality of the TCR Vbeta repertoire in CDR3 region could reflect T cell-mediated immunity.…”