EFSD CD3+CD56+ cells a novel human regulatory population: function and molecular mechanism in type 1 diabetes (DSB.AD001.091)
Project areaOncologia e Immunologia (DSB.AD001)
Structure responsible for the research project
Type 1 diabetes (T1D) results from autoimmune damage of insulin producing b cells in the pancreas. The disease is determined by a breakdown in the mechanisms that mediate immune tolerance, resulting in the expansion of islet-reactive CD4+ and CD8+ T effector (Teff) cells and subsequent b cell destruction. T cells with regulatory properties have been shown to play a key role in the pathogenesis of autoimmune disorders. However, to date, specific regulation of CD8+ T cell function is still largely unexplored. Recently we described that the absolute number of circulating CD3+CD56+ T cells represents a valuable predictive marker of b cell residual function up to one year after T1D diagnosis. Specifically, high CD3+CD56+ T cells numbers, at disease onset, associated with a higher ² cell activity in T1D one year later, suggesting a possible regulatory role for this subset in T1D pathogenesis. Our preliminary results show that freshly isolated human CD3+CD56+ cells (negative for Va24, typically expressed on iNKT cells) specifically modulate antigen-dependent activation of CD8+ T cells in vitro.
We have described that frequency of CD3+CD56+ cells are significantly associated with residual b cell function in children affected by type 1 diabetes (T1D) at diagnosis (Galgani M et al., 2013). Moreover, our preliminary data indicate a suppressive activity of CD3+CD56+ cells on CD8+ lymphocytes activated via antigen-specific T cell receptor (TCR). This proposal aims at investigating the role of CD3+CD56+ cells in the control of the immune imbalances that characterise T1D development by:
(a) Investigating the metabolic asset (glycolysis, mitochondrial respiration and b-oxidation) CD3+CD56+ cells and their phenotypic profile by analysing the expression of the main regulatory T cell-lineage markers (ie, CTLA-4 PD1, PD1 GITR, CD39, CD49d) and chemokine receptors (ie, CXCR4, CCR5, CCR; CCR5)
(b) Investigating the molecular mechanisms through which CD3+CD56+ mediate suppression of cytotoxicity and interferon (IFN)-g production by TCR stimulated CD8+ lymphocytes.
(c) Analysing, in a large cohort of T1D children at disease onset, the ability of of CD3+CD56+ cells to suppress effector function of effector CD8+ lymphocytes.
Start date of activity
Immune Tolerance, Type 1 diabetes, regulatory T cells
Last update: 04/12/2023