Monitoring immunomodulation strategies in type 1 diabetes

Abstract

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease. Short-term treatment with agents targeting T cells, B cells and inflammatory cytokines to modify the disease course resulted in a short-term pause in disease activity. Lessons learnt from these trials will be discussed in this review. It is expected that effective disease-modifying agents will become available for use in earlier stages of T1D. Progress has been made to analyze antigen-specific T cells with standardization of T cell assay and discovery of antigen epitopes but there are many challenges. High-dimensional profiling of gene, protein and TCR expression at single cell level with innovative computational tools should lead to novel biomarker discovery. With this, assays to detect, quantify and characterize the phenotype and function of antigen-specific T cells will continuously evolve. An improved understanding of T cell responses will help researchers and clinicians to better predict disease onset, and progression, and the therapeutic efficacy of interventions to prevent or arrest T1D.

Keywords: T cell exhaustion; antigen specific therapy; biomarkers; disease modifying treatment; type 1 diabetes.

Figure 1

T cell monitoring during immune intervention in type 1 diabetes: Ex vivo assays on peripheral blood mononuclear cells are utilised for assessing drug efficacy and monitoring therapeutic response in clinical intervention trials. Basic research to identify neo-epitopes targeted by T cells will make it possible to capture antigen-specific T cells more widely. High-dimensional analysis of gene, protein and TCR expression will identify novel markers expressed on T cells during different stages of the disease and in response to treatment. This information will be utilised to refine ex vivo peripheral blood analysis to detect, quantify, and characterise T cell populations.