ThG Cells: A Distinct T Helper Cell Subset with Lineage Characteristics

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 naive CD4+ T cells in vitro, suggesting that ThG cells in vivo also develop directly from naive 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.