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CD8+ T cell Exhaustion as T1D Biomarker

CD8+ T cell exhaustion rate predicts progression of T1D

Learning Objectives

  • Describe T cell exhaustion and explain its importance in T1D pathophysiology

Summary

CD8+ T cell exhaustion is a unique differentiation state, so not only terminal cells, but an exhausted cell has also reduced inflammatory function, which means it makes fewer inflammatory cytokines, and it has increased expression of inhibitory receptors, which facilitates this reduced function.

It makes sense if it's secreting fewer inflammatory cytokines that these cells, or more of these exhausted CD8+ T cells, would be beneficial for autoimmunity and the converse would be true for cancer. And that actually is the case. Many people in the field of cancer are trying to get rid of these cells.

We're trying to keep them, and so what we found in islet-specific CD8+ T cells, using TMR technology and cyTOF to read this out, is that CD8+ exhausted T cells are increased with age in both slow and rapid progressors. 

The slow progressors are in the darker colored circles, the rapid are in the lighter color and both of those exhausted cells in the total CD8+ population increase with age.

This makes complete sense. Exhaustion occurs with chronic antigen stimulation which does occur more and more with age. However, if we look within the islet-specific population, it is only the slow progressors that have the higher level of exhaustion, and this is regardless of the age of an individual. This points out the effect of exhaustion functionally.

MAT-GLB-2407835-1.0 - 12/2024