Autoreactive T effector memory differentiation mirrors ? cell function in type 1 diabetes.

ABSTRACT: In type 1 diabetes, cytotoxic CD8+ T cells with specificity for ? cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting ? cells. In contrast, the disease relevance of ? cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to ? cell function, are not known. Here, we tracked multiple, circulating ? cell-reactive CD8+ T cell subsets and measured ? cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in ? cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57- counterparts, and network association modeling indicated that the dynamics of ? cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating ? cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

SUBMITTER: Yeo L 

PROVIDER: S-EPMC6063477 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature