Phagocytosis, a potential mechanism for myeloid-derived suppressor cell regulation of CD8+ T cell function mediated through programmed cell death-1 and programmed cell death-1 ligand interaction

Young June Kim, Su Jung Park, Hal E. Broxmeyer

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

CD8+ T cells become exhausted, inducing cell surface protein programmed cell death-1 (PD-1) as chronic virus diseases or tumors progress, but underlying mechanisms of this are unclear. We previously showed that M-CSF is important for developing tolerogenic dendritic cells (DCs) from human CD14 + monocytes. In this article, we identify M-CSF-derived DCs (M-DCs) after stimulation with IL-10 as myeloid-derived suppressor cells with additional tolerogenic activities to CD8+ T cells. IL-10 increased PD-1 ligand expression on M-DC, and IL-10-stimulated M-DCs (M-DC/IL-10) induced expression of PD-1 on, and apoptosis of, CD8+ T cells and phagocytosed CD8 + T cells. Enhanced phagocytic activity of M-DC/IL-10 required IFN-γ, which further increased PD-1 ligand and PD-2 ligand expression on M-DC/IL-10. IFN-γ-stimulated M-DC/IL-10 cells were phenotypically macrophage-like cells with little or no expression of CD86, a costimulatory molecule, but with high expression levels of CD14, CD200R, and CD80. No phagocytic activity was detected with GM-CSF-derived DCs. We propose that phagocytosis by IFN-γ-stimulated M-DC/IL-10 cells, which may be DCs or, alternatively, a unique subset of macrophages, may be a mechanism by which IFN-γ-producing CD8+ T cells are tolerized after type 1 immune responses to chronic virus or tumor, and that IFN-γ links effector CD8+ T cells to their phagocytic clearance.

Original languageEnglish (US)
Pages (from-to)2291-2301
Number of pages11
JournalJournal of Immunology
Volume187
Issue number5
DOIs
StatePublished - Sep 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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