Abstract

IL-17-secreting T cells represent a distinct lineage of CD4+ T effector cells (Th17) essential in the pathogenesis of numerous inflammatory disorders, autoimmune diseases and tumor immunity. A means to define the population of human Th17 cells has been confounded by the heterogeneity and plasticity of helper and regulatory T cell subsets. Although combinations of chemokine and surface receptors have been associated with the Th17 phenotype, these markers are not unique to Th17 T cells. In this study, we adapt a murine-based strategy to enrich for a population of human IL-17-producting CD4 T cells from PBMC. Isolation of IL-17+ and IL-17-negative T cell clones provided uniform lineage-specific populations that enabled us to identify differentially expressed genes. Consistent with previously published data, enhanced expression of IL-23R, RORC and CCR4 were well-represented in IL-17+ CD4 T cell clones confirming their lineage specificity. A closer analysis of these clones reveals a functional phenotype that excludes Rhodamine and differentially expresses CCR6 and CD161. We extrapolate these findings to the unselected PBMC population and using a combination of surface and functional markers, demonstrate that a uniquely defined, non-destructive strategy can be used to enrich for IL-17+, Treg-resistant T cells; furthermore, antigen-specific IL-17+ effectors can be expanded using this approach to achieve numbers of cells sufficient for adoptive cellular therapy of cancer.

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