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

Abstract

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 lifelong 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 naïve (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 CCR7-EM 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.

Treg Heterogeneity, Function, and Homeostasis

“…Treg lymphocytes function in different tissues and inflammatory sites, which is why their differentiation is associated with the acquisition of corresponding chemokine receptors and adhesion molecules responsible for directed homing. Thus, CCR4 is for migration to the skin, GPR-15 is for migration to the intestines, and CXCR3, LFA-1, VLA-4, CCR2, CCR5, CCR6, CCR8 are for migration to inflammation zones (47)(48)(49).…”