title: Mucosal-associated invariant T cells are depleted and functionally altered in patients with common variable immunodeficiency.
abstract: Common variable immunodeficiency (CVID) is a primary immunoglobulin deficiency characterized by recurrent infections and complications, including autoimmunity, enteropathy, polyclonal lymphocytic infiltration or lymphoid malignancy. Innate T cells can support B cell maturation and antibody production. We investigated the numbers, phenotypes and functions of circulating B cell, γδ T cell, invariant natural killer T (iNKT) cell and mucosal-associated invariant T (MAIT) cell subsets in 23 CVID patients and 27 healthy controls. Switched-memory B cells and plasmablasts were depleted in CVID patients (p<0.0001). γδ T cells were found at normal numbers, but iNKT and MAIT cells were depleted (p<0.0001 and p<0.002). MAIT cells were especially low in patients with complicated CVID (p<0.05). MAIT cells from patients appeared more activated and more frequently produced interleukin-17A, interleukin-22 and tumor necrosis factor-α than MAIT cells from healthy subjects in vitro. Thus, MAIT cell depletion and activation may contribute to immunodeficiency and complications associated with CVID.
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Serena
authors.initials: S
authors.lastname: Arduini
authors.affiliation: Department of Immunology, St. James's Hospital, Dublin, Ireland.
authors.forename: Jean
authors.initials: J
authors.lastname: Dunne
authors.affiliation: Department of Immunology, St. James's Hospital, Dublin, Ireland.
authors.forename: Niall
authors.initials: N
authors.lastname: Conlon
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Immunology, St. James's Hospital, Dublin, Ireland.
authors.forename: Conleth
authors.initials: C
authors.lastname: Feighery
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland. Electronic address: derek.doherty@tcd.ie.
authors.forename: Derek G
authors.initials: DG
authors.lastname: Doherty
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count / Q000379:methods; D008297:Male; D008875:Middle Aged; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22
keywords: CVID; Innate immunity; MAIT cells; iNKT cells; γδ T cells