Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes.

The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses to drug in the weeks after treatment. Thus, we investigated whether early changes in T cell immunophenotypes could serve as biomarkers of drug activity.

Interconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8 T cells beneficial in type 1 diabetes.

Distinct Natural Killer (NK)-like CD57 and PD-1 CD8 exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins and relationships between these cell types are poorly understood. Here we show that while PD-1 and CD57 Tex populations are epigenetically similar, CD57 Tex cells display unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes.

Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.

Human type 1 diabetes (T1D) is caused by autoimmune attack on the insulin-producing pancreatic beta cells by islet antigen-reactive T cells. How human islet antigen-reactive (IAR) CD4+ memory T cells from peripheral blood affect T1D progression in the pancreas is poorly understood. Here, we aim to determine if IAR T cells in blood could be detected in pancreas.

Integrating Omics into Functional Biomarkers of Type 1 Diabetes.

Biomarkers are critical to the staging and diagnosis of type 1 diabetes (T1D). Functional biomarkers offer insights into T1D immunopathogenesis and are often revealed using "omics" approaches that integrate multiple measures to identify involved pathways and functions. Application of the omics biomarker discovery may enable personalized medicine approaches to circumvent the more recently appreciated heterogeneity of T1D progression and treatment.