Interplay between expression of PD-L1 on thyrocytes and intrathyroidal lymphocytes and FOXP3 as a marker of regulatory T lymphocytes in Hashimoto thyroiditis

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.<b>NEW & NOTEWORTHY</b> 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.