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Institut National de la Santé et de la Recherche Médicale Unité 437 and Institut de Transplantation et de Recherche en Transplantation, Nantes, France;
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; and
Department of Nephrology and Clinical Immunology, Nantes University Hospital, Nantes, France
Dendritic cells (DCs) are a rare population of leukocytes
specialized in Ag processing and presentation to T cells. We have
previously shown that cultured rat splenic DCs exhibit a cytotoxic
activity against selected target cells. In this study, we analyzed this
function in DCs freshly prepared from lymphoid organs using the
DC-specific OX62 mAb and magnetic beads. Freshly extracted splenic DCs,
but not lymph node and thymic DCs, exhibited a strong and moderate
cytotoxic activity against YAC-1 and K562 target cells, respectively.
FACS analyses showed that spleen contained a minor subset (1015%) of
CD4+ and class IIint DCs that also expressed
the OX41 Ag and the lymphoid-related Ags CD5 and CD90 (Thy-1) and a
major (8085%) subset of
CD4-/OX41-/CD5- and class
IIint DCs. The cytotoxic activity of splenic DCs was
strictly restricted to the CD4- DCs, a subset poorly
represented in LN and thymus. Contrasting with our previous report
using cultured splenic DCs, freshly isolated splenic DCs killed YAC-1
cells using a Ca2+-independent mechanism, but this function
did not appear mediated by Fas ligand, TNF-related apoptosis-inducing
ligand, or TNF-
. Therefore, rat DCs contain a subset of naturally
cytolytic cells that could play a role in both innate and acquired
immune responses. Together with our previous report, these data suggest
that rat DCs can use two mechanisms of cytotoxicity depending on their
maturation/activation state.
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