CD8+ T cell-dependent elimination of dendritic cells in vivo limits the induction of antitumor immunity.
The fate of dendritic cells (DC) after they have initiated a T cell immune response is still undefined. We have monitored the migration of DC labeled with a fluorescent tracer and injected s.c. into naive mice or into mice with an ongoing immune response. DC not loaded with Ag were detected in the draining lymph node in excess of 7 days after injection with maximum numbers detectable approximately 40 h after transfer. In contrast, DC that had been loaded with an MHC class I-binding peptide disappeared from the lymph node with kinetics that parallel the known kinetics of activation of CD8+ T cells to effector function. In the presence of high numbers of specific CTL precursors, as in TCR transgenic mice, DC numbers were significantly decreased by 72 h after injection. The rate of DC disappearance was extremely rapid and efficient in recently immunized mice and was slower in "memory" mice in which memory CD8+ cells needed to reacquire effector function before mediating DC elimination. We also show that CTL-mediated clearance of Ag-loaded DC has a notable effect on immune responses in vivo. Ag-specific CD8+ T cells failed to divide in response to Ag presented on a DC if the DC were targets of a pre-existing CTL response. The induction of antitumor immunity by tumor Ag-loaded DC was also impaired. Therefore, CTL-mediated clearance of Ag-loaded DC may serve as a negative feedback mechanism to limit the activity of DC within the lymph node.
Hermans
I F
IF
Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington, New Zealand.
Ritchie
D S
DS
Yang
J
J
Roberts
J M
JM
Ronchese
F
F
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C024098:6-carboxyfluorescein