{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:19:12Z","timestamp":1788261552890,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005343","name":"Fundaci\u00f3n IMSS","doi-asserted-by":"publisher","award":["R-2022-785-047."],"award-info":[{"award-number":["R-2022-785-047."]}],"id":[{"id":"10.13039\/501100005343","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by sustained immune activation and fluctuating disease activity. Although exhaustion-associated markers are frequently detected on T cells from patients with SLE, the biological significance of these signatures remains poorly defined. Here, we performed high-dimensional phenotypic profiling of circulating CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from patients with inactive and active SLE using spectral flow cytometry, complemented by an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of sustained TCR stimulation. We identified distinct T cell subsets characterized by coordinated expression of multiple immune checkpoint receptors, including PD-1, LAG-3, TIM-3, TIGIT and CD39, together with the transcriptional regulator TOX. Notably, checkpoint-enriched populations were preferentially expanded in patients with active disease (aSLE). Despite the accumulation of inhibitory features, both CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells retained effector-associated features, including cytokine production and cytotoxic mediator expression, suggesting that immune checkpoint expression in this context is not uniformly associated with the complete loss of effector-associated features characteristic of canonical T cell exhaustion. Trajectory inference of\n                    <jats:italic>ex vivo<\/jats:italic>\n                    datasets, together with the\n                    <jats:italic>in vitro<\/jats:italic>\n                    model, suggested an association between sustained activation and increasing immune checkpoint receptor expression while maintaining the expression of effector-associated molecules. Collectively, these findings identify distinct checkpoint-enriched T cell phenotypic states in SLE, in which immune checkpoint receptor expression coexists with retained effector-associated features. Overall, this work provides a framework for interpreting immune checkpoint-associated T cell phenotypes in systemic autoimmunity.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1818795","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:58:57Z","timestamp":1788260337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Checkpoint-enriched T cells with retained effector-associated features are associated with disease activity in systemic lupus erythematosus"],"prefix":"10.3389","volume":"17","author":[{"given":"Paola","family":"Santana-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Doctorado en Ciencias Biol\u00f3gicas y de la Salud, Universidad Aut\u00f3noma Metropolitana","place":["Mexico City, Mexico"]},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, Unidad M\u00e9dica de Alta Especialidad (UMAE) Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n A.","family":"Gaj\u00f3n","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, Unidad M\u00e9dica de Alta Especialidad (UMAE) Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social","place":["Mexico City, Mexico"]},{"name":"Posgrado en Ciencias Bioqu\u00edmicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid Asminda","family":"Ram\u00edrez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Unidad M\u00e9dica de Alta Especialidad (UMAE) Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Victoria","family":"Legorreta-Haquet","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, Unidad M\u00e9dica de Alta Especialidad (UMAE) Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Manuel","family":"Amezcua-Guerra","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Bonifaz","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunoqu\u00edmica, Unidad M\u00e9dica de Alta Especialidad (UMAE) Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social","place":["Mexico City, Mexico"]},{"name":"Coordinaci\u00f3n de Investigaci\u00f3n en Salud, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Karina","family":"Ch\u00e1vez-Rueda","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, Unidad M\u00e9dica de Alta Especialidad (UMAE) Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00398-2","article-title":"Systemic lupus 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