IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors

Inhibitory receptors (IR) are a diverse group of cell surface molecules that modulate T cell activation, but there are gaps in our knowledge of the cell-extrinsic factors that regulate their expression. The present study found that in vivo overexpression of IL-27 in mice led to increased T cell expr...

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Veröffentlicht in:ImmunoHorizons 2019-01, Vol.3 (1), p.13-25
Hauptverfasser: DeLong, Jonathan H, O'Hara Hall, Aisling, Rausch, Matt, Moodley, Devapregasan, Perry, Joseph, Park, Jeongho, Phan, Anthony T, Beiting, Daniel P, Kedl, Ross M, Hill, Jonathan A, Hunter, Christopher A
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Sprache:eng
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Zusammenfassung:Inhibitory receptors (IR) are a diverse group of cell surface molecules that modulate T cell activation, but there are gaps in our knowledge of the cell-extrinsic factors that regulate their expression. The present study found that in vivo overexpression of IL-27 in mice led to increased T cell expression of PD-L1, LAG-3, TIGIT, and TIM-3. In vitro, TCR stimulation alone promoted expression of multiple IRs, whereas IL-27 alone induced expression of PD-L1. However, the combination of intermediate TCR stimulation and IL-27 resulted in synergistic induction of LAG-3, CTLA-4, and TIGIT. In vivo, infection with resulted in parasite-specific effector T cells that expressed high levels of IR, and at local sites of infection where IL-27 production was highest, IL-27 was required for maximal effector cell expression of PD-L1, LAG-3, CTLA-4, and TIGIT. Together, these results affirm the critical role of TCR signals in the induction of IR expression but find that during infection, IL-27 promotes T cell expression of IR.
ISSN:2573-7732
2573-7732
DOI:10.4049/immunohorizons.1800083