Phenotypically defined subpopulations of circulating follicular helper T cells in common variable immunodeficiency

Abstract

Background: Common variable immunodeficiency (CVID) is characterized by low immunoglobulin G and IgA/IgM, decreased switched memory B cells, impaired response to vaccine, and an increased susceptibility to infections and autoimmunity. T_FH cells play an important role in germinal center reaction where it supports isotype switching, somatic hypermutation, generation of memory B cells, and differentiation of B cells to plasma cells. The objective was to study the distribution of three subsets of T_FH cells and their relationship with autoimmune diseases associated with CVID.

Methods: T_FH cells have been divided into T_FH 1 (interleukin 21 [IL-21] and interferon γ), T_FH 2 (IL-21 and IL-4), and T_FH 17 (IL-21 and IL-17) cells. Mononuclear cells from 25 patients with CVID and age and gender-matched controls were stained with various monoclonal antibodies (anti-CD4 APC, anti-CXCR5 FITC, anti-CCR6 PerCP, and anti-CXCR3 PE) and isotype controls and analyzed for T_FH 1 (CD4⁺ CXCR5⁺ CXCR3⁺ CCR6^- ), T_FH 2 (CD4⁺ CXCR5⁺ CXCR3^- CCR6^- ), and T_FH 17 (CD4⁺ CXCR5⁺ CXCR3^- CCR6⁺ ) cells by multicolor flow cytometry. Twenty thousand cells were acquired and analyzed by FlowJo software. Statistical analysis of comparison of patients and healthy controls was performed by paired t test using PRISM 7 software.

Results: T_FH 2 and T_FH 17 cells subpopulations of T_FH cells were significantly decreased (P < .003 and P < .006, respectively) in CVID as compared with controls. No significant difference was observed in any of T_FH cell subpopulations between CVID with and those without autoimmunity group.

Conclusion: Alterations in T_FH cell subpopulation may play a role in defects in B cell compartment in CVID.

Keywords: CVID; autoimmunity; follicular helper T cells.

Figure 1

T_FH cell subsets in CVID and controls. Mononuclear cells from 25 CVID patients and healthy controls were stained with monoclonal antibodies and isotype. CVID, common variable immunodeficiency

Figure 2

T_FH cell subsets relations to autoimmune diseases in CVID. T_FH1, T_FH2, and T_FH17 subsets and T_FH1/T_FH17 ratio were compared for CVID patients with autoimmune diseases (n = 7) and without autoimmune diseases (n = 18). CVID, common variable immunodeficiency