We analysed blood samples from multiple patients with type 1 diabetes collected at six-month intervals over two years. We used optimised protocols to track changes in populations of autoreactive CD8 T cells in blood, and novel technologies to further characterise them.
Successfully, this work led us to a novel finding: we discovered that changes in autoreactive CD8 T cell populations positively correlated with changes in the β cell function, i.e. as β cell function decreases T cell levels decrease, and vice versa. The T cell population was defined by the expression of the marker CD57, or more specifically by CD57+ effector memory CD8+ T cell population. This finding means we identified a T cell population in the blood of patients with type 1 diabetes that is directly linked with ongoing β cell death in the pancreas.
To pursue this discovery and further characterise the T cell population of interest, we isolated CD57+, and CD57– T cells as a control population, from the blood of five individuals with type 1 diabetes and five healthy controls, and analysed the gene expression profile. We isolated the RNA from the samples and sequenced it. We observed that CD57+ cells showed a significant enrichment of expression of genes associated with cytotoxicity, compared with their CD57– counterparts, indicating a gene signature associated with enhanced effector function and immunogenicity. Data indicated that CD57+ cells are highly differentiated and antigen-experienced, capable of exerting immediate cytotoxic effects.
To better understand the differentiation pathway of the CD57+ cells, we studied the epigenetic landscape characterising the accessible regions of the chromatin in four individuals with type 1 diabetes and four healthy controls. In addition, we characterised the T cell receptor and RNA expression at single cell level in CD57+ T cells from two individuals with type 1 diabetes. We believe these results will help to identify key mechanisms involved in the differentiation and regulation of the CD57+ T cells, having a high impact in the understanding of the disease progression. Data are still under analysis.
