Neutrophil involvement in cross-priming CD8+ T cell responses to bacterial antigens.
Substantial CD8(+) T cell responses are generated after infection of mice with recombinant Listeria monocytogenes strains expressing a model epitope (lymphocytic choriomeningitis virus NP(118-126)) in secreted and nonsecreted forms. L. monocytogenes gains access to the cytosol of infected cells, where secreted Ags can be accessed by the endogenous MHC class I presentation pathway. However, the route of presentation of the nonsecreted Ag in vivo remains undefined. In this study we show that neutrophil-enriched peritoneal exudate cells from L. monocytogenes-infected mice can serve as substrates for in vitro cross-presentation of both nonsecreted and secreted Ag by dendritic cells as well as for in vivo cross-priming of CD8(+) T cells. In addition, specific neutrophil depletion in vivo by low dose treatment with either of two Ly6G-specific mAb substantially decreased the relative CD8(+) T cell response against the nonsecreted, but not the secreted, Ag compared with control Ab-treated mice. Thus, neutrophils not only provide rapid innate defense against infection, but also contribute to shaping the specificity and breadth of the CD8(+) T cell response. In addition, cross-presentation of bacterial Ags from neutrophils may explain how CD8(+) T cell responses are generated against Ags from extracellular bacterial pathogens.
Tvinnereim
Amy R
AR
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Hamilton
Sara E
SE
Harty
John T
JT
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology; D001202:Ascitic Fluid / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured / Q000276:immunology; D003433:Crosses, Genetic; D003600:Cytosol / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007111:Immunity, Cellular; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000637:transplantation; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000950:Antigens, Ly; D006183:H-2 Antigens; C480309:Ly6G antigen, mouse; D009698:Nucleoproteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus