A subset of cytolytic dendritic cells in rat.
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 (10-15%) of CD4(+) and class II(int) DCs that also expressed the OX41 Ag and the lymphoid-related Ags CD5 and CD90 (Thy-1) and a major (80-85%) subset of CD4(-)/OX41(-)/CD5(-) and class II(int) 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 Ca(2+)-independent mechanism, but this function did not appear mediated by Fas ligand, TNF-related apoptosis-inducing ligand, or TNF-alpha. 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.
Trinité
B
B
Institut National de la Santé et de la Recherche Médicale Unité 437 and Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
Voisine
C
C
Yagita
H
H
Josien
R
R
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D015704:CD4 Antigens / Q000096:biosynthesis; D002460:Cell Line; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D053222:Fas Ligand Protein; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D007940:Leukemia L5178; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D015704:CD4 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008024:Ligands; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; C505655:Tnfsf10 protein, rat; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D054353:Perforin