γδ T cells are crucial effectors of antibacterial response in T2D complicated with diabetic foot

Nearly half a billion people worldwide have type 2 diabetes (T2D), which poorly controlled may lead to severe consequences, including diabetic foot. Growing evidence highlights the role of γδ T subsets in the antibacterial response. A total of 70 patients were divided into three groups: T2D, T2D with diabetic foot (DF), and individuals without T2D. Flow cytometry was used to assess the frequency of peripheral blood γδ T along with activation (CD69, CD56) and senescence (CD57) markers. Intracellular expression of cytokines was tested on peripheral γδ T and Vδ2 in vitro cultures. PBMCs were stimulated with S. aureus and P. aeruginosa lysates and the expression of CD25, HLA-DR, along with CD137, CD154 on Vδ1 and Vδ2 cells was determined.  The predominance of the Vδ2 was observed in DF group. γδ T cells in DF patients were significantly activated, as evidenced by CD69 and CD56 expression. Moreover, upon phosphoantigen stimulation, both peripheral and zoledronate-derived Vδ2 exhibited increased levels of intracellular IL-17A and TNF compared to patients without T2D. The γδ T cell responses to bacterial lysates were more pronounced in Vδ2 than in Vδ1 cells within the DF group. Among Vδ1 cells more of them were CD137 positive than Vδ2. Overall, the data show differentiated antibacterial properties of Vδ1 and Vδ2 cells in T2D patients. Understanding of the role of γδ T cell subpopulations may improve the prevention of T2D complications.