Single-Cell Analysis of CD4 T Cells in Type 1 Diabetes: From Mouse to Man, How to Perform Mechanistic Studies

Type 1 diabetes is the prototypical CD4 T cell–mediated autoimmune disease. Its genetic linkage to a single polymorphism at position 57 of the HLA class II DQβ chain makes it unique to study the molecular link between HLA and disease. However, investigating this relationship has been limited by a series of anatomical barriers, the small size and dispersion of the insulin-producing organ, and the scarcity of appropriate techniques and reagents to interrogate antigen-specific CD4 T cells both in man and rodent models. Over the past few years, single-cell technologies, paired with new biostatistical methods, have changed this landscape. Using these tools, we have identified the first molecular link between MHC class II and the onset of type 1 diabetes. The translation of these observations to man is within reach using similar approaches and the lessons learned from rodent models.