Previous reports have demonstrated abnormalities in cellular immunity on CVID pathogenesis that affect activation and proliferation of T cells and, consequently, B cell differentiation and production of antibody 
. However, there are few studies examining the influence of Tregs in CVID subjects 
We observed that our patients presented significantly higher levels of CD8+ T cell activation. The percentage of Tregs expressing CD25highFOXP3+ was found to be lower in CVID subjects compared to controls but no significant association between Treg cells and immune activation was observed in these patients.
One of the greatest difficulties in studying Tregs is to select the combination of markers that best describe these subsets and currently the most common markers used to define these cells are CD25high
and FOXP3+ 
. The absence of IL-7R (CD127) on CD4 T cells has proven to be a reliable delineator of selection for Treg cells with the highest suppressive function 
. Our results using these markers are in line with previous reports, showing a reduced number of Treg cells in CVID patients 
. It is important to emphasize that these results were observed in a small group of Brazilian patients with different demographic and clinical characteristics to European subjects, which suggests that the proportion of Tregs could be directly related to this immunodeficiency.
Fevang et al. described that CVID patients with splenomegaly had a lower proportion of Tregs compared to others CVID patients 
, as our study, just included one patient with splenomegaly, this suggests that others clinical complications must be associated with reduced Treg population. One topic for further discussion is whether this low percentage is the cause or consequence of clinical complications observed in CVID patients.
No differences were observed in Tregs frequency when comparing CVID patients with and without AID. Despite preliminary studies having suggested an association between these cells and AID in CVID 
, it has not been established and can be influenced by other associated clinical complications that affect not only the frequency, but the profile of cytokine secreted by Tregs.
All patients analyzed were being treated with IVIG and, the correlation between Tregs and IVIG has already been described showed and expansion of Tregs in animal models 
, however we observed a reduced frequency of these cells in CVID subjects. Also, it has been demonstrated that Tregs increases the intracellular expression of TGF-β, IL-10 and FOXP3 following the addition of IVIG 
, but unfortunately we did not analyze the cytokine secretion by Tregs in our patients.
Furthermore, considering the increase of T cell markers activation in CVID subjects, specially CD8+ T cells, without a significant increase in IFN-g production, we suggest that these cells could have a suppressor function, according to previous reports and this result probably was unaffected by IVIG replacement 
. The similar percentage of cells expressing proliferation marker (Ki67) between the two groups could reflect the absence of lymphoproliferative disease in our sample, since contrasting results have been described in the literature 
To summarize, this paper shows that CD25highFOXP3+CD127low expressing Treg cells were lower in CVID patients, which suggests that Tregs cells can be impaired in CVID, thus having influence on the mechanism pathogenic of this complex immunodeficiency.