Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo

Summary Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. Abnormalities of CD4 + CD25 high forkhead box P3 (FoxP3) + regulatory T cells (T reg ) have been associated with autoimmune and inflammatory disorders, and we hypothesized that CVID might be characterized by T reg abnormalities. CD3 + cells from patients and controls were analysed for the expression of FoxP3 mRNA by real time reverse transcription–polymerase chain reaction (RT–PCR). Peripheral blood mononuclear cells from CVID patients and controls were stained for T reg markers, analysed by flow cytometry and compared to clinical characteristics. The main findings were: (i) CVID patients had significantly decreased expression of FoxP3 mRNA and decreased proportions of CD4 + CD25 high FoxP3 + cells compared to controls; (ii) CVID patients with splenomegaly had even lower proportions of T reg compared to other patients and controls; (iii) serum levels of the inflammatory marker neopterin were correlated negatively with the proportions of T reg within the CVID population, while there was no significant association with bronchiectasis. We have demonstrated decreased proportions of T reg in CVID patients, particularly in those with signs of chronic inflammation. Decreased proportions of T Reg are suggested to be pathogenetically important in autoimmunity, and our results suggest that T Reg may have a similar role in CVID.