title: Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7.
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 perforin-expressing imDCs was also detected in various lymphoid tissues in normal animals and its frequency was markedly enhanced after GM-CSF administration.
authors: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors: Lior
authors: L
authors: Zangi
authors: Yael Zlotnikov
authors: YZ
authors: Klionsky
authors: Liran
authors: L
authors: Yarimi
authors: Esther
authors: E
authors: Bachar-Lustig
authors: Yaki
authors: Y
authors: Eidelstein
authors: Elias
authors: E
authors: Shezen
authors: David
authors: D
authors: Hagin
authors: Yumi
authors: Y
authors: Ito
authors: Toshiyuki
authors: T
authors: Takai
authors: Shlomit
authors: S
authors: Reich-Zeliger
authors: Assaf
authors: A
authors: Lask
authors: Oren
authors: O
authors: Milstein
authors: Steffen
authors: S
authors: Jung
authors: Vera
authors: V
authors: Shinder
authors: Yair
authors: Y
authors: Reisner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054353:Perforin / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D019061:src-Family Kinases / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D054353:Perforin; D019061:src-Family Kinases; D053804:Granzymes