Human T cells modulate myeloid-derived suppressor cells through a TNF-α-mediated mechanism

Markus Bauswein, Anurag Singh, Anjali Ralhan, Davide Neri, Katharina Fuchs, Kelly Daryll Blanz, Iris Schäfer, Andreas Hector, Rupert Handgretinger, Dominik Hartl, Nikolaus Rieber

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Myeloid-derived suppressor cells (MDSC) represent an innate immune cell subset capable of suppressing T-cell responses in cancer and chronic inflammation. While the effect of MDSC on T cells has been defined thoroughly, the reciprocal impact of T cells on MDSC homeostasis remains poorly understood. Therefore, we comprehensively analyzed the effect of different T-cell subsets on the generation and survival of human MDSC. Using an in vitro MDSC generation assay, we demonstrate that unstimulated CD4 + , but not CD8 + T cells, induce polymorphonuclear MDSC (PMN-MDSC) from CD33 + myeloid cells. This effect was dependent on direct cell-cell contact and required TNF-α signaling. Soluble TNF-α was dispensable for PMN-MDSC generation, suggesting that transmembrane TNF-α is involved in that trans-cellular process. Stimulated human CD3 + T cells delayed the apoptosis of PMN-MDSC, which was independent of TNF-α signaling or direct cell-cell contact, but was recapitulated by IL-2. Taken together, our study shows that human T cells modulate MDSC generation and survival through two distinct mechanisms and thereby fine-tune the homeostasis of human MDSC in a regulated manner.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalImmunology Letters
Volume202
DOIs
StatePublished - Oct 2018
Externally publishedYes

Keywords

  • Apoptosis
  • Crosstalk
  • IL-2
  • MDSC
  • Myeloid-derived suppressor cells
  • PMN-MDSC
  • Reciprocal
  • T cells
  • TNF-alpha
  • TNF-α

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