Abstract
ABSTRACTIn mice, γδ T cells that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage in the thymus, and in the periphery, these cells play a critical role in host defence and anti-tumor immunity. Unlike αβ T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that immature CD27+Ly6C—cells convert into mature CD27+Ly6C+cells, and these mature cells control cancer progression while the immature cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+cells and human Vδ2+cells, while IL-27 is dispensable for mouse CD27+Ly6C—cells and human Vδ1+cells. These data reveal increased complexity within IFNγ-producing γδ T cells, comprising of immature and terminally differentiated subsets, that offer new insights into unconventional T cell biology.ONE SENTENCE SUMMARYCD27+Ly6C—γδ T cells differentiate into CD27+Ly6C+γδ T cells that are maintained by IL-27 to counteract cancer progression.IMPORTANTManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way.Upon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor.The identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report.The identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred.GUIDELINESFor reviewers:https://www.reviewcommons.org/reviewersFor authors:https://www.reviewcommons.org/authorsCONTACTThe Review Commons office can be contacted directly at:office@reviewcommons.org
Publisher
Cold Spring Harbor Laboratory