Phenotypic Analysis of CD4+ Treg, CD8+ Treg, and Breg Cells in Adult Common Variable Immunodeficiency Patients

Abstract

Introduction: Regulatory lymphocytes (CD4+ T regulatory cells [Treg], CD8+ Treg, and B regulatory cells [Breg]) play a critical role in immune homeostasis and tolerance. Common variable immunodeficiency (CVID) is associated with increased susceptibility to infections and increased frequency of inflammatory and autoimmune diseases. CD4+ Treg cell abnormalities have been reported in CVID; however, CD8+ Treg cells have not been reported in CVID. The objective of this study was to evaluate CD4+ Treg and CD8+ Treg cells in CVID patients. Methods: In 25 patients with CVID and age-matched healthy controls, Treg cells, evaluated in freshly isolated peripheral blood mononuclear cells (natural; nCD4+ Treg and nCD8+ Treg) and following in vitro activation with anti-CD3/CD28 monoclonal antibodies (induced; iCD4+ Treg and iCD8+ Treg) as well as Breg cells were analyzed with specific monoclonal antibodies and isotype controls using flow cytometry. Results: The proportions of nCD4+ Treg (CD4+ CD127^low CD25^high FoxP3+), iCD4+ Treg (CD4+ CD127^low CD25^high FoxP3+), iCD8+ Treg (CD8+ CD25^high CD183+ FoxP3+), and Breg (CD19+ CD24^high CD38^high) lymphocytes were significantly lower in patients with CVID than in controls. Conclusions: Altered regulatory lymphocytes may play a role in the pathogenesis and autoimmunity and inflammation associated with CVID.