Similarities and singularities between innate-like T cell subsets in adults with type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease for which mouse models have highlighted a role for innate-like T cells, although evidence in humans remains limited. Here, we integrated for the first time flow cytometry analyses of invariant natural killer T (iNKT), γδT, and mucosal-associated invariant T (MAIT) cells from the same adults with recent-onset T1D (n = 21), long-term T1D (n = 47), and healthy controls (n = 55). Recent-onset T1D was associated with reduced frequencies of TNFα-producing iNKT and γδT cells, whereas long-term T1D showed more pronounced alterations, including increased PD-1 expression and an exhaustion-like phenotype across all three populations. Principal-component analysis integrating iNKT, γδT, and MAIT cell parameters positioned recent-onset patients between healthy controls and long-term T1D patients. Exploratory predictive modeling suggests that MAIT cell markers may contribute to disease classification. Together, these findings provide an integrated view of innate-like T cell alterations in adult T1D and highlight their relationship with disease duration.