BackgroundLow-grade systemic inflammation is considered to participate in the progression of type 2 diabetes (T2D) and in diabetic complications.MethodsTo determine if circulating leukocytes were abnormally regulated in T2D patients, 8-color flow-cytometry (FACS) analysis was performed in a cross-sectional study of 37 T2D patients and 16 controls. Data obtained from the FACS analysis were compared to coronary flow reserve (CFR), assessed by Rb82-PET-imaging, to uncover inflammatory signatures associated with impaired CFR.ResultsPresence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R+, Treg’s and TLR4+ T cells, while the monocyte population showed enhanced TLR4 expression. Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR. In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.ConclusionsOur demonstration that HbA1c inversely correlates to several T cell populations suggests that T cells may play disease modulating roles in T2D. Further, the novel association between impaired CFR and regulatory T cells and IL-21R+ T cells imply an intricate balance in maintaining tissue homeostasis in vascular diabetic complications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0378-5) contains supplementary material, which is available to authorized users.