{"id":27115,"date":"2025-03-12T23:50:23","date_gmt":"2025-03-12T22:50:23","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/03\/12\/early-expansion-of-tigitpd1-effector-memory-cd4-t-cells-via-agonistic-effect-of-alefacept-in-new-onset-type-1-diabetes\/"},"modified":"2025-03-12T23:50:23","modified_gmt":"2025-03-12T22:50:23","slug":"early-expansion-of-tigitpd1-effector-memory-cd4-t-cells-via-agonistic-effect-of-alefacept-in-new-onset-type-1-diabetes","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/03\/12\/early-expansion-of-tigitpd1-effector-memory-cd4-t-cells-via-agonistic-effect-of-alefacept-in-new-onset-type-1-diabetes\/","title":{"rendered":"Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jan 1;214(1):12-22. doi: 10.1093\/jimmun\/vkae014.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses to drug in the weeks after treatment. Thus, we investigated whether early changes in T cell immunophenotypes could serve as biomarkers of drug activity. We characterized T cell responses by flow cytometry and identified an exhausted-like population of CD2low CD4 effector memory T cells coexpressing TIGIT and PD1 that expanded by 11 wk after the start of treatment. This population was not entirely spared from alefacept-mediated depletion in vivo or in vitro but recovered through homeostatic proliferation of CD2low cells in vivo. Proliferation of TIGIT+PD1+ effector memory CD4 T cells increased with treatment, with a concomitant reduction of proinflammatory cytokine production. The persistent increase of TIGIT+PD1+ effector memory CD4 T cells was specific to alefacept treatment; 2 other T cell depleting therapies, teplizumab and anti-thymocyte globulin, induced only a transient increase in this CD4 population. Our data suggest that the expanding TIGIT+PD1+ effector memory CD4 T cell population represents a promising biomarker of early treatment effects of alefacept. The nondepleting effects on proliferation and cytokine production also suggest agonistic activity by this CD2 targeted therapy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40073269\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250312185022&amp;v=2.18.0.post9+e462414\">40073269<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkae014\">10.1093\/jimmun\/vkae014<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jan 1;214(1):12-22. doi: 10.1093\/jimmun\/vkae014. ABSTRACT The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses &#8230; <a title=\"Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/03\/12\/early-expansion-of-tigitpd1-effector-memory-cd4-t-cells-via-agonistic-effect-of-alefacept-in-new-onset-type-1-diabetes\/\" aria-label=\"Read more about Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes\">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":[42,71],"tags":[],"class_list":["post-27115","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/27115","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=27115"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/27115\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=27115"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=27115"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=27115"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}