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In response to Manuscript AJRI 01‐18‐016 entitled “Regulatory T cells, natural killer cells and obesity in patients with gestational diabetes mellitus”—Kawada T

We thank Dr. Kawada1 for his interest in our new publication.2 Dr. Kawada mentions a recently published review on this topic by Bonamachi and Lee,3 but according to these authors, there are few studies investigating the role of natural killer (NK) cells on the development of obesityinduced inflammation and insulin resistance (IR). We evaluated subsets of regulatory T (Treg) and NK cells in peripheral blood of overweight women with Gestational Diabetes Mellitus (GDM). As we mentioned in our article, there are a few other studies on GDM that evaluated similar cellular subpopulations but using different markers.4-6 The Bonamachi and Lee3 review presented interesting results on NK cells and other cell populations (innate lymphoid cells and invariant NKT cells) but mostly in experimental studies and do not mention any studies involving pregnant women nor patients with GDM. Dr. Kawada states that CD4Treg and other T lymphocytes subpopulations “play an important role in the regulation of obesityinduced inflammation in visceral adipose tissue,” thus “subclinical glucose intolerance had already been recognized in obese subjects.” In addition, Dr. Kawada points out that CD8T cells increase with obesity in blood and adipose tissue and their inhibition could be related to the prevention of metabolic disorders. Although some investigators reported these findings, the profile of immune cells in peripheral blood in obese individuals with or without metabolic disorders remains controversial.7 Different studies have reported the existence of Tcells subsets and NK cells not in all obese (body index mass—BMI >30 kg/m2) patients, but only in those with morbid obesity (BMI >40 kg/m2) and metabolic alterations.7-10 van der Weerd et al8 reported increased numbers of CD4T lymphocytes with predominance of Treg (T CD4+ CD25+ FoxP3+) subset, but normal number of CD8T cells in peripheral blood of adults with morbid obesity without metabolic alterations. On the other hand, Sen et al9 found a significant decrease in circulating CD8T cells in healthy obese pregnant women, but no difference in CD4T population. According to Han et al,10 obesity did not affect the immune response of young adults; however, these individuals had a lower number of CD8T lymphocytes in their peripheral blood. We evaluated subsets of Treg and NK cells defined by specific cell markers in overweight pregnant women with and without GDM, and we found significant differences that seem to be related with the development of IR and inflammation. Our patients were mostly overweight (BMI ≥25 kg/m2) but not obese, and had mild, wellcontrolled GDM (only with diet); we recognize that is a limitation of our study and may explain why we did not find more significant changes. In addition, Dr. Kawada reported some data on the expression of perforin, granzyme, and granulysin on CD8T lymphocytes of peripheral blood and adipose tissue. We detected increased percentages of circulating NK cells with cytotoxic profile, but we did not investigate lymphocytes in adipose tissue, nor did we assess the expression of these toxins; therefore, we cannot speculate about its relation with overweight and GDM. Finally, we agree with Dr. Kawada that the effect of impaired Treg and NK cell profile on GDM should be confirmed in a prospective study. We recommend that this future study should include more participants with higher BMIs and a group of women with more severe forms of GDM who require insulin for their treatment.