Characterization of Antigen-Induced CD4+ T-Cell Senescence in Multiple Sclerosis

Frontiers in Neurology

Marco Puthenparampil¹  Carolina Cruciani²  Paula Tomas-Ojer²  Roland Martin²  María José Docampo²  Mireia Sospedra² 

[1] Department of Neuroscience DNS, University-Hospital of Padova, Padova, Italy;Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital and University Zurich, Zurich, Switzerland;

关键词: multiple sclerosis (MS);    CD4;    T-cell;    T-cell senescence;    regulation;   

DOI  :  10.3389/fneur.2022.790884

来源: DOAJ

【 摘 要 】

Antigen-induced T-cell exhaustion and T-cell senescence are peripheral regulatory mechanisms that control effector T-cell responses. Markers of exhaustion and senescence on T Cells indicate the previous activation by repetitive stimulation with specific antigens. Malignant tumors are accompanied by enhanced T-cell exhaustion and T-cell senescence resulting in immune evasion, while these control mechanisms might be diminished in autoimmune diseases including multiple sclerosis (MS). To better understand the involvement of antigen-induced T-cell senescence in controlling CD4+ T-cell-mediated autoimmune responses in MS, we have analyzed the re-expression of CD45RA and the downregulation of CD28 and CD27 molecules as markers of antigen-induced T-cell senescence in fresh cerebrospinal fluid (CSF)-infiltrating and paired circulating T cells from patients with MS. Patients with different levels of CD4+ T-cell senescence were identified and characterized regarding demographical and clinical features as well as intrathecal markers of neurodegeneration. CD4+ T-cell senescence was also analyzed in control patients to explore a putative deficit of this regulatory mechanism in MS. This study shows heterogeneity of markers of CD4+ T-cell senescence in patients with MS. Patients with high levels of CD4+ T-cell senescence in peripheral blood showed increased frequencies of CSF-infiltrating CD28+ CD27-EM CD4+ T cells with a proinflammatory Th1 functional phenotype. The correlation of these cells with the intrathecal levels of neurofilament light chain, a marker of neurodegeneration, suggests their relevance in disease pathogenesis and the involvement of T-cell senescence in their regulation. Markers of antigen-induced T-senescence, therefore, show promise as a tool to identify pathogenic CD4+ T cells in patients with MS.

【 授权许可】

Unknown