Type 1 Diabetes (T1D) is a disease characterized by a lymphocyte-mediated destruction of insulin-producing beta-cells in genetically susceptible individuals. It has been demonstrated that lymphocytes with regulatory properties are essential for the maintenance of tolerance against self-tissues (pancreas) and alterations in the number and functions of these cells have been correlated with the break of immune tolerance.
We have recently shown that the frequency, in the blood, of a lymphocyte population co-expressing CD56 and CD3 molecules (here defined as CD3+CD56+ cells), represents a valuable predictive marker of T1D progression (Galgani M et al. 2013). Preliminary data show that the absolute number and percentage of CD3+CD56+ cells are significantly reduced in the blood of a large cohort of new-onset T1D subjects compared with sex and age-related healthy individuals. In addition, the frequency of CD3+CD56+ lymphocytes in the blood positively correlated with good glycaemic control and fasting C- peptide in recent-onset T1D children (see later). Finally, additional studies have been showing that CD3+CD56+ cells, isolated from healthy controls, suppress the activity of triggered lymphocytes involved in pancreas damage; of note, this activity was impaired in CD3+CD56+ cells isolated from the blood of T1D subjects.
We assume that number and function of CD3+CD56+ cells may serve as biological markers to monitor disease progression, in autoimmune diabetes. Functional defects of this “regulatory” cell subset could account for the exaggerate function of lymphocytes in T1D. Thus, the results of this proposal may pave the way to the better characterization of a novel cell population involved in the T1D pathogenesis, likely representing a useful biomarker potentially implicated in the control of the immune tolerance.