부산대학교 도서관

In type 1 diabetes, cytotoxic [CD8.sup.+] T cells with specificity for [beta] cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting [beta] cells. In contrast, the disease relevance of [beta] cell-reactive [CD8.sup.+] T cells that are detectable in the circulation, and their relationship to [beta] cell function, are not known. Here, we tracked multiple, circulating [beta] cell-reactive [CD8.sup.+] T cell subsets and measured [beta] cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in [beta] cell-specific effector memory [CD8.sup.+] T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive [CD57.sup.+] effector memory [CD8.sup.+] 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.sup.-] counterparts, and network association modeling indicated that the dynamics of [beta] cell-reactive [CD57.sup.+] effector memory [CD8.sup.+] T cell subsets were strongly linked. Thus, coordinated changes in circulating [beta] cell-specific [CD8.sup.+] T cells within the [CD57.sup.+] 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.
Introduction Type 1 diabetes is an autoimmune disease in which insulin-secreting [beta] cells of the pancreatic islets are selectively destroyed (1, 2). [CD8.sup.+] T cells are regarded as critical players [...]