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

Medicine (Baltimore). 2016 Jul;95(30):e4304. doi: 10.1097/MD.0000000000004304.

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.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Common Variable Immunodeficiency / drug therapy
  • Common Variable Immunodeficiency / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / therapeutic use
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*
  • Treatment Outcome

Substances

  • Immunoglobulin A
  • Immunoglobulin G