Limited infiltration of exogenous dendritic cells and naive T cells restricts immune responses in peripheral lymph nodes.
Primary CD8 T cell responses in lymph nodes (LN) and protective immunological tumor control are quantitatively limited following immunization with exogenous peptide-pulsed dendritic cells (DC). This arises from two constraints. First, LN are saturated by relatively small quantities of exogenous DC. Second, circulation of new naive T cells into DC-infiltrated LN during the functional lifespan of the DC is negligible. Limits on DC and T cellularity in, and flux through, LN constrain the magnitude of both primary and subsequent recall responses. Enhanced immune responses and tumor control can be achieved using maneuvers to augment LN retention of DC or availability of naive T cells to Ag-presenting DC. These data offer an increased understanding of LN function in general and provide a practical basis for improvements in tumor immunotherapy.
Department of Microbiology, Carter Immunology Center, University of Virginia Health System, Charlottesville, VA 22908, USA.
David W
DW
Mullins
Victor H
VH
Engelhard
D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006183:H-2 Antigens / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics; D015789:HLA-A2 Antigen; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D006183:H-2 Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D064532:Histocompatibility Antigen H-2D; D011993:Recombinant Fusion Proteins