Immune imbalance in rheumatoid arthritis: insights from γδ T cell receptor phenotyping

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. While conventional αβ T cells have been extensively studied, the contribution of γδ T cells to RA pathogenesis remains insufficiently understood. Unlike αβ T cells, γδ T cells recognize antigens independently of major histocompatibility complex (MHC) restriction, and their surface receptor expression plays a pivotal role in regulating effector functions. This study aimed to investigate the phenotype and surface receptor profile of γδ T cells in RA patients undergoing anti-TNF therapy, to better understand their potential immunoregulatory and prognostic significance. Peripheral blood samples were collected from RA patients before and during treatment with TNF inhibitors, as well as from healthy controls. Flow cytometry was used to quantify γδ T cell frequency and to assess the expression of selected activation, differentiation, and exhaustion markers on their surface. RA patients exhibited a significant reduction in the frequency of circulating γδ T cells compared with healthy controls. Moreover, γδ T cells in RA displayed phenotypic features of advanced differentiation and functional exhaustion, including altered expression of key surface receptors. The observed alterations in γδ T cell phenotype and receptor expression suggest chronic immune activation in RA. These findings highlight the potential of γδ T cell surface markers as candidate biomarkers for disease activity and response to anti-TNF therapy.