Deletion of cognate CD8 T cells by immature dendritic cells: A novel role for perforin, granzyme A, TREM-1, and TLR7

Lior Zangi, Yael Zlotnikov Klionsky, Liran Yarimi, Esther Bachar-Lustig, Yaki Eidelstein, Elias Shezen, David Hagin, Yumi Ito, Toshiyuki Takai, Shlomit Reich-Zeliger, Assaf Lask, Oren Milstein, Steffen Jung, Vera Shinder, Yair Reisner

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Immature dendritic cells (imDCs) can have a tolerizing effect under normal conditions or after transplantation. However, because of the significant heterogeneity of this cell population, it is extremely difficult to study the mechanisms that mediate the tolerance induced or to harness the application of imDCs for clinical use. In the present study, we describe the generation of a highly defined population of imDCs from hematopoietic progenitors and the direct visualization of the fate of TCR-transgenic alloreactive CD4+ and CD8+ T cells after encountering cognate or noncognate imDCs. Whereas CD4+ T cells were deleted via an MHC-independent mechanism through the NO system, CD8+ T-cell deletion was found to occur through a unique MHC-dependent, perforin-based killing mechanism involving activation of TLR7 and signaling through Triggering Receptor-1 Expressed on Myeloid cells (TREM-1). This novel subpopulation of perforinexpressing imDCs was also detected in various lymphoid tissues in normal animals and its frequency was markedly enhanced after GM-CSF administration.

Original languageEnglish
Pages (from-to)1647-1657
Number of pages11
JournalBlood
Volume120
Issue number8
DOIs
Publication statusPublished - 2012 Aug 23

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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