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 (T) 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 T and a reduced central T cell population when compared to GM untreated group. An increase in the frequencies of TNFα, IL-2, and IL-17 CD8 T cells was observed whereas only TNFαCD4 T 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.
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http://dx.doi.org/10.3389/fimmu.2019.00887 | DOI Listing |
Mol Med
January 2025
Center for Autoimmune Musculoskeletal and Hematopoietic Diseases, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, New York, 11030, USA.
Background: The process of B cell activation and plasma cell (PC) formation involves morphological, transcriptional, and metabolic changes in the B cell. Blocking or reducing PC differentiation is one approach to treat autoimmune diseases that are characterized by the presence of pathogenic autoantibodies. Recent studies have suggested the potential of myricetin, a natural flavonoid with anti-inflammatory and antioxidant properties, to block or reduce PC differentiation.
View Article and Find Full Text PDFNat Immunol
January 2025
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Mucosal antigen-specific T cells are pivotal for pathogen clearance and immune modulation in respiratory infections. Dysregulated T cell responses exacerbate coronavirus disease 2019 severity, marked by cytokine storms and respiratory failure. Despite extensive description in peripheral blood, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells in the lungs remain elusive.
View Article and Find Full Text PDFCommun Biol
January 2025
Large Molecules Research, Sanofi, Cambridge, MA, USA.
Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, D genes were thought to recombine only in the forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us to question whether these symmetrical sequences might enable bidirectional recombination.
View Article and Find Full Text PDFSci Rep
January 2025
State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China.
Cytokines play pivotal roles in anticancer immune response. We previously reported that adenovirus armed with an IL18 variant (DR18) that overcomes IL18BP neutralizing effect displayed powerful therapeutic effects in local and distant tumors when delivered intratumorally. Here, we tested a combined delivery of IL12 and DR18 in tumor models since IL12 and IL18 are known to act synergistically in potentiating IFNγ production and antitumor immunity.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Rapa Therapeutics, Rockville, Maryland, USA.
Background: Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (T) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.
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