GSE216679 Reduced CD8 T cell exhaustion in DR4 risk subjects is selectively augmented with therapy [CD8s]

Contributors : S A Long ; Virginia S Muir ; Britta E Jones ; Valerie Z Wall ; Katharina Lambert ; Alyssa Ylescipidez ; Stephan Pribitzer ; Jerill Thorpe ; Bryce Fuchs ; Alice E Wiedeman ; Megan Tatum ; Hannes Uchtenhagen ; Cate Speake ; Bernard Ng ; Alexander T Heubeck ; Troy R Torgerson ; Adam K Savage ; Michael A Maldonado ; Neelanjana Ray ; Vadim Khaychuk ; Jinqi Liu ; Peter S Linsley ; Jane H BucknerSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensExhausted CD8 T cells (TEX) are associated with worse outcome in cancer yet better outcome in autoimmunity. However, factors contributing to reduced TEX in autoimmunity are poorly understood. We use two genetically related autoimmune diseases, type 1 diabetes (T1D) and rheumatoid arthritis (RA), to explore these factors. We identify a common human peripheral blood TIGIT+KLRG1+ CD8 TEX population: TIGIT+KLRG1+ CD8 TEX of healthy controls (HC), T1D, and rheumatoid arthritis (RA) subjects share EOMES signature genes, are increased with age and in chronic viral-specific cells and are hyporesponsive in vitro. Consistent with a genetic determinant, TIGIT+KLRG1+ TEX are stable within but vary between individuals. In HC and RA subjects (n>100/cohort), lower levels of EOMES transcriptional modules and TIGIT+KLRG1+ TEX were associated with RA HLA risk alleles (DR0401, 0404, 0405, 0408, 1001) even when considering disease status and CMV seropositivity. TIGIT+KLRG1+ TEX significantly incr...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research