CD8⁺ Treg cells play a role in the obesity-associated insulin resistance

Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4⁺ Treg cells. However, little is known about the CD8⁺ Treg cells. Therefore, we aim to characterize the CD8⁺ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre- and post-bariatric surgery. A group of age- and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8⁺ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8⁺ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1- and Tc1/17-like CD8⁺ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8⁺ Tregs infiltrated, compared to PB or VAT, while CD8⁺ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3⁺CD8⁺ Tregs in circulation, and PD-1⁺CD8⁺ Tregs infiltrated in the VAT. An increase in the percentage of circulating Tc1-like CD8⁺ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8⁺ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.