![\"Divergent](\"https:\/\/onlinelibrary.wiley.com\/cms\/asset\/82c4fecb-f493-4aa0-90d0-75513ef29b66\/eji70093-gra-0001-m.png\")
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How chronic immune stimulations differentially shape CD4\u207a T cell senescence remains unclear. Using high-dimensional mass cytometry and functional profiling, we show that cytomegalovirus (CMV) drives expansion of cytotoxic CD27\u2212<\/sup>CD28\u2212<\/sup> CD4\u207a T cells, whereas rheumatoid arthritis (RA) exerts nonredundant effects by modulating their effector capacity.<\/p>\n <\/p>\n Chronic antigen exposure drives CD4\u207a T cell senescence, yet how autoimmunity and persistent viral infections differentially shape T cell differentiation and function remains unclear. Using cytomegalovirus (CMV) and rheumatoid arthritis (RA) as models of chronic immune activation, we performed high-dimensional mass cytometry and functional assays to define their impact on CD4\u207a T cells. In CMV-seropositive individuals, CD27\u2212<\/sup>CD28\u2212<\/sup> CD4\u207a T cells were abundant and exhibited a predominantly cytotoxic, nonproliferative phenotype. Only a minor fraction was CMV-reactive, suggesting that bystander-driven differentiation contributes to this subset. In the absence of CMV, senescent CD4\u207a T cells were infrequent and phenotypically distinct, though they still exhibited low proliferative capacity. EBV and HSV did not independently increase CD27\u2212<\/sup>CD28\u2212<\/sup> CD4\u207a T cell frequency. Similarly, RA had little effect on their abundance but instead tuned the functional quality of senescent cells. In CMV-seropositive RA patients, senescent CD4\u207a T cells produced less pro-inflammatory cytokines and showed impaired cytotoxic degranulation. Central memory CD4\u207a and CD27\u2212<\/sup>CD28\u2212<\/sup> CD8\u207a T cell functions were preserved, with no evidence for CMV reactivation, suggesting maintained viral control by unaffected T cell responses. These findings highlight distinct, nonredundant effects of CMV and RA on CD4\u207a T cell senescence and reveal RA-specific functional defects in senescent CD4\u207a T cells.<\/p>","protected":false},"excerpt":{"rendered":" How chronic immune stimulations differentially shape CD4\u207a T cell senescence remains unclear. Using high-dimensional mass cytometry and functional profiling, we show that cytomegalovirus (CMV) drives expansion of cytotoxic CD27\u2212CD28\u2212 CD4\u207a T cells, whereas rheumatoid arthritis (RA) exerts nonredundant effects by modulating their effector capacity. ABSTRACT Chronic antigen exposure drives CD4\u207a T cell senescence, yet how … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[112,42],"tags":[],"class_list":["post-48837","post","type-post","status-publish","format-standard","hentry","category-european-journal-of-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/48837","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=48837"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/48837\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=48837"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=48837"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=48837"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}ABSTRACT<\/h2>\n