TY - JOUR
T1 - Deletion of cognate CD8 T cells by immature dendritic cells
T2 - A novel role for perforin, granzyme A, TREM-1, and TLR7
AU - Zangi, Lior
AU - Klionsky, Yael Zlotnikov
AU - Yarimi, Liran
AU - Bachar-Lustig, Esther
AU - Eidelstein, Yaki
AU - Shezen, Elias
AU - Hagin, David
AU - Ito, Yumi
AU - Takai, Toshiyuki
AU - Reich-Zeliger, Shlomit
AU - Lask, Assaf
AU - Milstein, Oren
AU - Jung, Steffen
AU - Shinder, Vera
AU - Reisner, Yair
PY - 2012/8/23
Y1 - 2012/8/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865418252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865418252&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-02-410803
DO - 10.1182/blood-2012-02-410803
M3 - Article
C2 - 22776817
AN - SCOPUS:84865418252
SN - 0006-4971
VL - 120
SP - 1647
EP - 1657
JO - Blood
JF - Blood
IS - 8
ER -