Chronically Activated T-cells Retain Their Inflammatory Properties in Common Variable Immunodeficiency.

Autor: Berbers RM; Department of Rheumatology and Clinical Immunology, University Medical Center and Utrecht University, Utrecht, The Netherlands., van der Wal MM; Center for Translational Immunology, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands., van Montfrans JM; Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands., Ellerbroek PM; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands., Dalm VASH; Department of Internal Medicine, Division of Clinical Immunology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Immunology, Academic Center for Rare Immunological Diseases (RIDC), Erasmus MC University Medical Center, Rotterdam, The Netherlands., van Hagen PM; Department of Internal Medicine, Division of Clinical Immunology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Immunology, Academic Center for Rare Immunological Diseases (RIDC), Erasmus MC University Medical Center, Rotterdam, The Netherlands., Leavis HL; Department of Rheumatology and Clinical Immunology, University Medical Center and Utrecht University, Utrecht, The Netherlands. h.leavis@umcutrecht.nl., van Wijk F; Center for Translational Immunology, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2021 Oct; Vol. 41 (7), pp. 1621-1632. Date of Electronic Publication: 2021 Jul 11.
DOI: 10.1007/s10875-021-01084-6
Abstrakt: Purpose: 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).
Methods: 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.
Results: Both CD4 + and CD8 + T-cells in CVIDid showed an increased activation profile (HLA-DR + , Ki67 + , IFNγ +) when compared to CVIDio, with concomitant upregulation of negative regulators of immune activation PD1, LAG3, CTLA4, and TIGIT. PD1 + and LAG3 + subpopulations contained equal or increased frequencies of cells with the capacity to produce IFNγ, 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 + effector Tregs. Increased migratory capacity to inflamed and mucosal tissue was also observed in CVIDid T-cells.
Conclusion: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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