Home > Immunology Assays > T Cell Exhaustion Assay
Assays for measuring reversal of CD4 and CD8 T cell exhaustion by checkpoint inhibitors and cytokines The reduction in T cell responsiveness as a result of chronic exposure to antigen is of considerable importance in infectious diseases and cancers. We have built up a high-throughput assay platform suitable for exploring modulators of T cell exhaustion based on a period of sustained T cell activation (to induce ‘exhaustion’) where markers of exhaustion are upregulated (A), followed by a subsequent stimulation (B). The clinically validated immuno-oncology agent pembrolizumab reverses the ‘unresponsive’ phenotype demonstrating a large assay window (C). Subsets of exhausted T cells (sorted on the basis of markers) can provide more ‘resistant’ populations to investigate. Finally antigen-recall responses can be used to model an ‘exhausted’ response in freshly isolated cells (D).
Assays may be suitable for evaluating modulators of 4-1BB, CD3, CD27, CD28, CD40, CD40L, CD70, CD80, CD86, CTLA-4, JAK1, JAK2, JAK3, GITR, ICOS, ICOSL, IL-2R, IL-9R, IL-21R, LAG-3, OX40, OX40L, PD-1, PDL-1, STAT1, STAT3, STAT5, TCF-1, TGFb, TIGIT, TIM-3, and others.
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