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A striking example is chronic inflammatory demyelinating polyneuropathy (CIDP), a CD4+ T cell-mediated autoimmune disease of the peripheral nervous system, which has a peak decade of onset of 70-79 years. How aging predisposes to autoimmunity, however, remains unclear. CD4+ T cells are highly susceptible to age-associated changes, including acquisition of immunosenescent features such as enhanced SA-\u03b2-gal activity, increased Cdkn1a (p21) expression, and upregulation of Tnfsf8 (CD153). We show here that CD4+ T cells exhibiting these changes are increased in CIDP patients and mice with CIDP-like disease. These CD4+ T cells exhibit a senescence-associated secretory phenotype (SASP), show functional senescence (i.e., decreased proliferation and resistance to apoptosis), and have enhanced capacity for inciting neuropathy. Notably, a senescent cell-clearing senolytic agent (fisetin) decreased the pathogenic capacity of CD4+ T cells, and a SASP-suppressing senomorphic therapy (ruxolitinib) protected mice against autoimmune demyelination. Together, these findings delineate a key role for age-associated senescent CD4+ T cells in driving age-associated autoimmunity.<\/jats:p>","DOI":"10.64898\/2026.01.07.698250","type":"posted-content","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T21:25:14Z","timestamp":1767907514000},"source":"Crossref","is-referenced-by-count":0,"title":["Age-associated Autoimmunity Driven by T cell Immunosenescence"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-2366","authenticated-orcid":false,"given":"Ethan C.","family":"McCarthy","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9315-9544","authenticated-orcid":false,"given":"Maryamsadat","family":"Seyedsadr","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison F.","family":"Bang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn L. 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