Autoreactive T cells in type 1 diabetes

Autoimmune type 1 diabetes is considered a T cell mediated disease in which autoreactive CD4 and CD8 effector T cells destroy insulin-producing β-cells located in pancreatic islets, leading to life-long dependence on exogenous insulin. Surprisingly, islet reactive CD4 effector T cells can also be found in the blood of non-diabetic individuals.

This suggests that autoreactive effector T cells from T1D subjects are more pathogenic than healthy controls or that islet reactive regulatory T cells in T1D patients fail to suppress the function of effector cells.  To address this question, the Cerosaletti lab is studying islet reactive CD4 effector and regulatory T cells using high dimensional flow cytometry coupled with single cell RNA sequencing to capture their gene expression profiles and T cell receptor sequences. This approach is coupled with technology to determine what islet proteins are recognized by individual islet reactive T cells.  

These studies have led to the identification of expanded clones of islet reactive CD4 effector T cells with innate-like features that are expanded at the time of disease onset. The lab is currently investigating whether these innate-like islet reactive T cells are linked to disease progression.

We have also identified a unique subset of proinflammatory islet reactive CD4 effector T cells at disease onset that is linked to the response to immunotherapy in a T1D clinical trial.

In parallel, the lab is studying the gene expression profile, T cell receptor repertoire and specificity of islet reactive regulatory T cells in T1D patients compared with non-diabetic donors to understand how these cells differ in T1D.