The Children’s Hospital of Philadelphia - Center for Applied Genomics; University of Pennsylvania - Department of Pediatrics; University of Pennsylvania - Division of Human Genetics
Using single-cell RNA-seq and high-dimensional single-cell mass cytometry (CyTOF), we identified eight distinct populations of antigen-experienced CD45RA-CD4+ T cells in peripheral blood of healthy donors. In addition to Tregs and established Th lineages, we also identified a distinct population of T cells that lacked expression of master transcription factors and signature cytokines of other Th cell lineages. These cells, which we tentatively designated “ThG”, were a subset of GM-CSF+ Th cells distinct from GM-CSF+ Th1, Th2, Th9, Th17 and Th22 cells. ThG cells co-expressed GM-CSF, IL-2, TNF, IL-3 and CCL20. They were also present in mice. Both human and mouse ThG cells can be efficiently differentiated from naïve CD4+ T cells in vitro, suggesting that ThG cells in vivo also develop directly from naïve precursors. ThG cells had a stable phenotype and were highly encephalitogenic. Similar to Th17 cells, ThG cells switched their phenotype to Th1 in response to IL-12. T-bet was not required for ThG development, but it was required for their encephalitogenicity. Analogous to other Th cells, ThG cells had a tendency to eventually cease GM-CSF expression without other major changes in their phenotype. These findings demonstrate that there are, both in humans and mice, ThG cells with stable phenotype that constitute a distinct population with lineage characteristics.
Rasouli, Javad and Casella, Giacomo and Yoshimura, Satoshi and Zhang, Weifeng and Xiao, Dan and Kumar, Gaurav and Garifallou, James and Gonzalez, Michael V. and Wiedeman, Alice and Mari, Elisabeth R. and Tang, Hsin-Yao and Fortina, Paolo and Hakonarson, Hakon and Long, Alice and Zhang, Guang-Xian and Ciric, Bogoljub and Rostami, Abdolmohamad, ThG Cells: A Distinct T Helper Cell Subset with Lineage Characteristics (November 4, 2019). Available at SSRN: https://ssrn.com/abstract=3498568 or http://dx.doi.org/10.2139/ssrn.3498568
This version of the paper has not been formally peer reviewed.
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