Abstract
TNFα inhibitors have shaped the landscape of rheumatoid arthritis (RA) therapy with high clinical efficiency. However, their impact on T cell recall responses is not well-elucidated. We aimed to analyze the immune profiles of memory T cells in RA patients undergoing TNFα inhibitor Golimumab (GM) treatment. Frequencies of peripheral T cell subsets and cytokine expression profiles in memory T cells (TM) upon PMA/Ionomycine stimulation were determined by flow cytometry. Antigen-specific CD8 T cell immunity was analyzed through stimulating PBMCs with CMV-EBV-Flu (CEF) viral peptide pool and subsequent intracellular IFNγ staining. Both peripheral CD8 and CD4 T cells from GM treated patients had a shift pattern characterized by an enlarged effector TM and a reduced central TM cell population when compared to GM untreated group. An increase in the frequencies of TNFα+, IL-2+, and IL-17+ CD8 TM cells was observed whereas only TNFα+CD4 TM cells increased in GM treated patients. Moreover, GM treated patients contained more peripheral IFNγ-producing CD8 T cells specific to CEF viral peptides. Together, these results show a distinct T cell subset pattern and enhanced memory T cell immunity upon GM treatment, suggesting an immunoregulatory effect of TNF inhibitor Golimumab on peripheral memory T cell responses.
Highlights
Rheumatoid arthritis (RA) is an inflammatory joint disease that is characterized by a chronic inflammatory reaction in the synovium of joints with sustained release of inflammatory cytokines [1, 2]
Patients and healthy controls (HCs) were matched for age and gender, GM treated patients and untreated ones were matched for clinical duration
The absence of significant differences in the inflammatory markers represented by ESR and C-reactive protein (CRP) between the GM untreated and GM treated group indicate that the inflammatory milieu is comparable between both groups
Summary
Rheumatoid arthritis (RA) is an inflammatory joint disease that is characterized by a chronic inflammatory reaction in the synovium of joints with sustained release of inflammatory cytokines [1, 2]. Tumor necrosis factor α (TNFα) has been postulated to be a main cytokine in RA pathogenesis that is responsible for the clinical manifestations of the disease [3] It is produced mainly by monocytes, macrophages and to a lesser degree by T cells [3]. Along with the development and clinical application of first biological agent Infliximab, TNFα inhibitors (TNFIs) become a major advancement in the treatment of RA [5] They are endowed with profound immunoregulatory effects and possess high clinical efficacy in ameliorating clinical symptoms as well as retarding tissue damages when used in combination with methotrexate (MTX) [5, 6]. No studies to date have investigated the functionality of memory T cells (TM) cells during TNFα blockade in RA
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