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Accession IconSRP079213

Innate to adaptive: Human IFN-gamma producing CD4+ T cells can derive directly from CXCL8-producing recent thymic emigrants.

Organism Icon Homo sapiens
Sample Icon 384 Downloadable Samples
Technology Badge IconNextSeq 500

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An unanticipated feature of the human neonatal CD4 T cell response is a robust capacity to produce CXCL8. However, this ''innate-like'' function dissipates with age and is scarce in the adult. Here, we investigated the fate of CD4+CXCL8+ cells and their transition into conventional adaptive T cells. We show that CXCL8 is imprinted on immature thymocytes prior to TCR signalling and is maintained in T cell committed thymic progenitors and recent thymic emigrants (RTEs) of adults as well as neonates. Hence, rather than being unique to neonates, CXCL8-producing CD4+ T cells decrease with age in humans (and in humanised mice) owing to the decline in thymic output, coupled with the cells' peripheral expansion. By cloning of CXCL8+CD4+ cells from cord blood, we were able to track effector function within daughter cells and demonstrate that these cells can convert to IFN-g producing cells. In sum, we provide direct evidence that 'innate like' CXCL8-producing CD4+ T cells emerge from the thymus and can transition into conventional adaptive Th1 cells Overall design: Examination of RNA-Seq count data from 96 single cells
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384
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