title: Inversion of the Vδ1 to Vδ2 γδ T cell ratio in CVID is not restored by IVIg and is associated with immune activation and exhaustion.
abstract: Common variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on γδ T cells in CVID patients. Newly diagnosed CVID patients (n = 15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study γδ T cells and CVID patients were compared to healthy controls (n = 22). The frequency and absolute count of Vδ1 γδ T cells was found to be increased in CVID (median 0.60% vs 2.64%, P <0.01 and 7.5 vs 39, P <0.01 respectively), while they were decreased for Vδ2 γδ T cells (median, 2.36% vs 0.74%, P <0.01 and 37.8 vs 13.9, P <0.01 respectively) resulting in an inversion of the Vδ1 to Vδ2 ratio (0.24 vs 1.4, P <0.001). Markers of immune activation were elevated on all subsets of γδ T cells, and HLA-DR expression was associated with an expansion of Vδ1 γδ T cells (r = 0.73, P = 0.003). Elevated PD-1 expression was found only on Vδ2 γδ T cells (median 1.15% vs 3.08%, P <0.001) and was associated with the decrease of Vδ2 γδ T cells (r = -0.67, P = 0.007). IVIg had no effect on the frequency of Vδ1 and Vδ2 γδ T cells or HLA-DR expression, but alleviated CD38 expression on Vδ1 γδ T cells (median MFI 965 vs 736, P <0.05). These findings suggest that immunological perturbations of γδ T cells are a general feature associated with CVID and are only partially reversed by IVIg therapy.
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa, São Paulo, Brazil.
authors.forename: Dominic
authors.initials: D
authors.lastname: Paquin-Proulx
authors.forename: Nathália Silveira
authors.initials: NS
authors.lastname: Barsotti
authors.forename: Bianca A N
authors.initials: BAN
authors.lastname: Santos
authors.forename: Ana Karolina B B
authors.initials: AKBB
authors.lastname: Marinho
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Kokron
authors.forename: Karina I
authors.initials: KI
authors.lastname: Carvalho
authors.forename: Myrthes T
authors.initials: MT
authors.lastname: Barros
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D017074:Common Variable Immunodeficiency / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G