{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:49:47Z","timestamp":1787946587880,"version":"build-2784847793"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T00:00:00Z","timestamp":1625961600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T00:00:00Z","timestamp":1625961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008955","name":"Wilhelmina Kinderziekenhuis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Immune dysregulation complications cause significant morbidity and mortality in common variable immunodeficiency (CVID), but the underlying pathophysiology is poorly understood. While CVID is primarily considered a B-cell defect, resulting in the characteristic hypogammaglobulinemia, T-cells may also contribute to immune dysregulation complications. Here, we aim to further characterize T-cell activation and regulation in CVID with immune dysregulation (CVIDid).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Flow cytometry was performed to investigate T-cell differentiation, activation and intracellular cytokine production, negative regulators of immune activation, regulatory T-cells (Treg), and homing markers in 12 healthy controls, 12 CVID patients with infections only (CVIDio), and 20 CVIDid patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Both CD4\u2009+\u2009and CD8\u2009+\u2009T-cells in CVIDid showed an increased activation profile (HLA-DR\u2009+\u2009, Ki67\u2009+\u2009, IFN\u03b3\u2009+) when compared to CVIDio, with concomitant upregulation of negative regulators of immune activation PD1, LAG3, CTLA4, and TIGIT. PD1\u2009+\u2009and LAG3\u2009+\u2009subpopulations contained equal or increased frequencies of cells with the capacity to produce IFN\u03b3, Ki67, and\/or GzmB. The expression of PD1 correlated with serum levels of CXCL9, 10, and 11. Treg frequencies were normal to high in CVIDid, but CVIDid Tregs had reduced CTLA-4 expression, especially on CD27\u2009+\u2009effector Tregs. Increased migratory capacity to inflamed and mucosal tissue was also observed in CVIDid T-cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>CVIDid was characterized by chronic activation of peripheral T-cells with preserved inflammatory potential rather than functional exhaustion, and increased tissue migratory capacity. While Treg numbers were normal in CVIDid Tregs, low levels of CTLA-4 indicate possible Treg dysfunction. Combined studies of T-cell dysfunction and circulating inflammatory proteins may direct future treatment strategies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10875-021-01084-6","type":"journal-article","created":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T02:02:12Z","timestamp":1625968932000},"page":"1621-1632","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Chronically Activated T-cells Retain Their Inflammatory Properties in Common Variable Immunodeficiency"],"prefix":"10.1007","volume":"41","author":[{"given":"Roos-Marijn","family":"Berbers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Written informed consent was obtained from all patients and controls according to the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"PH reports research grants and personal fees from Shire\/Takeda and CSL Behring. VD reports research grants and personal fees from Shire\/Takeda, Griffols, Actelion, Novartis, Pharming, and CSL Behring. JM reports personal fees from Shire\/Takeda. HL reports research grants from Shire\/Takeda. All other authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}