Interplay between expression of PD-L1 on thyrocytes and intrathyroidal lymphocytes and FOXP3 as a marker of...

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease marked by lymphocytic infiltration and progressive destruction of the thyroid gland. The pathogenesis involves cytotoxic T lymphocytes, whereas regulatory T cells (Tregs), identified by the transcription factor Forkhead box P3 (FOXP3), are crucial for maintaining self-tolerance. This study aimed to investigate the composition of HT' lymphocyte infiltrate and the expression of FOXP3 and PD-L1 within HT patients' thyroid tissue, aiming to clarify their roles in this chronically activated immune environment. This cross-sectional study analyzed surgical thyroid specimens from 18 patients with HT and 12 nonautoimmune controls. Immunohistochemistry was used to evaluate the expression of CD4⁺, CD8⁺, CD20⁺, FOXP3, and PD-L1 markers in the tissue. The HT group had significantly higher expression of CD4⁺, CD8⁺, and CD20⁺ lymphocytes. Although CD25⁺ expression was similar between groups, FOXP3 was positive in 100% of HT samples versus only 8.3% of controls. HT was associated with PD-L1 follicular cell expression in both the cytoplasm and cell membrane, a pattern distinct from the predominantly cytoplasmic expression in controls. In conclusion, this study demonstrates that HT involves a dense intrathyroidal infiltrate of effector T cells, B cells, and FOXP3⁺ Treg cells. The higher prevalence of FOXP3 without a corresponding higher prevalence of CD25⁺ suggests a population of chronically activated Tregs within the inflamed gland. The distinct expression pattern of PD-L1 in follicular cells indicates that the PD-1/PD-L1 pathway is actively engaged, possibly as a protective feedback mechanism against autoimmune destruction. These findings help clarify the local immunoregulatory network in HT and highlight Tregs and the PD-1/PD-L1 axis as promising targets for future therapeutic interventions.NEW & NOTEWORTHY This study provides insight into the local immune environment of Hashimoto's thyroiditis by analyzing the lymphocytic infiltrate in thyroid tissue directly. Key novel findings are the increased prevalence of FOXP3⁺ lymphocytes without a corresponding increase in CD25⁺ cells, suggesting a population of chronically activated regulatory T cells. It also identifies a distinct PD-L1 expression pattern in follicular cells (both membrane and cytoplasm), suggesting a protective feedback mechanism against autoimmune attack.