Pathogenic and Regulatory T Cells in Type 1 Diabetes: Losing Self-Control, Restoring It, and How to Take the Temperature

Abstract

The central role of T cells in type 1 diabetes pathogenesis is well established, but these cells continue to pose numerous challenges in understanding their dynamics and in following their modifications. Important progress has been recently made in pinpointing some novel antigens targeted by pathogenic T cells and the epitope sequences recognized. Studies on the interplay between effector T cells, their regulatory counterparts, and cells of the innate immune system have unraveled novel pathways and may inspire new therapeutic approaches. At the same time, the appreciation of the plasticity of regulatory T cells has raised important caveats on their use for cell-based therapies. Continuous development of T-cell assays exploring both pathogenic and regulatory players will be critical to "take the temperature" of undergoing disease progression and reversal.

Experiments by nature: lessons on type 1 diabetes

“…T cells reactive to several islet autoantigens have been indentified in humans . Although it is generally accepted that T cells have a role during the disease process, the possible function of B cells and autoAb in T1D in humans has not been completely resolved.…”

Isolation strategies of regulatory T cells for clinical trials: Phenotype, function, stability, and expansion capacity

“…Furthermore, results from animal models and clinical studies have clearly demonstrated that Treg deficiency and/or functional defects might contribute to the pathophysiology of aplastic anemia [25] and idiopathic thrombocytopenia [26,27], of autoimmune diseases like type-1 diabetes [28,29], multiple sclerosis [30], rheumatoid arthritis [30], as well as organ transplant rejection [31,32] and thus represent potential targets of Treg cell therapy (Table 3).…”

Biomarkers for immune intervention trials in type 1 diabetes

“…It appears that in nondiabetic individuals, potentially pathogenic T cells are held in check by various Tregdependent mechanisms. T1D may develop due, at least in part, to a defect (either functional or numerical) in the Treg repertoire or resilience of islet-reactive T cells to be suppressed[71]. Due to side effects associated with long-term generalized immunosuppression, the induction and maintenance of long-lasting tolerance specific to islet Ags remains a major focus for T1D clinical trials.…”