Regulatory T Cells with Effector Memory Phenotype and Glycaemic Control in Adult Type 1 Diabetes Mellitus

Background: There is controversy about absolute number, frequency, and status of homing markersof regulatory T (Treg) cells in patients with type 1 diabetes. We observed recently a considerable accumulation of terminally differentiated central memory subsets among CD4(+) and CD8(+) T cell expressing CD26 in patients with type 1 diabetes. The increased number of terminally differentiated central memory cells, which was positively associated with HbA1c levels, could suggest life-long stimulation by protracted antigen exposure or a homeostatic defect in the regulation/contraction of immune responses. Methods: We have analysed the phenotype of peripheral blood Treg cells in adult patients with type 1 diabetes using an 8-color flow cytometry assay panel for the characterisation of CD4(+)CD25(high)CD127-Treg cells into naive (N, CCR7(+)CD45RA(+)), central memory (CM, CCR7(+)CD45RA(-)), and effector memory (EM, CCR7-CD45RA(-)) cells. We also examined the expression of two additional markers: the serine protease CD26 that has been recently suggested as a negative selection marker for human Treg cells, and the cutaneous lymphocyte-associated antigen, given that the bidirectional homing of Treg cells between the skin and lymph nodes is important for efficient regulation. Results: We found that patients with type 1 diabetes had normal Treg frequencies but a low proportion of CCR7EM Treg cells, which was inversely correlated with both a long-term indicator of glycaemic control such as HbA1c and an indicator of renal function such as plasma creatinine. Conclusion: In our opinion, present results seem to support the second of the two initial hypotheses, i.e. a defect in regulation/suppression of immune homeostasis in diabetic people. Moreover, the worse glycaemic control (evaluated by HbA1c), the higher frequency of immune defects and more severe.