Interconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8+ T cells beneficial in type 1 diabetes.

Autor: Witkop, Erin M., Diggins, Kirsten, Wiedeman, Alice, Serti, Elisavet, Nepom, Gerald, Gersuk, Vivian H., Fuchs, Bryce, Long, S. Alice, Linsley, Peter S.
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Zdroj: Communications Biology; 6/27/2024, Vol. 7 Issue 1, p1-14, 14p
Abstrakt: Distinct Natural Killer (NK)-like CD57+ and PD-1+ CD8+ exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins and relationships between these cell types are poorly understood. Here we show that while PD-1+ and CD57+ Tex populations are epigenetically similar, CD57+ Tex cells display unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1+ and CD57+ Tex also show reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57+ Tex show unappreciated gene expression heterogeneity and share clonal relationships with PD-1+ Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1+, Tex-CD57+, Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex-like populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment. RNA-sequencing data from NK-like CD57+ and PD-1+ CD8+ exhausted-like T cell populations linked to beneficial immunotherapy response in autoimmune patients suggest shared clonal relationships with each other and with common precursor populations. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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