Neutrophils efficiently cross-prime naive T cells in vivo.
Neutrophils are professional phagocytes that migrate early, in high number, to the infection sites. Our study has analyzed how neutrophils cross-present antigens and influence CD8+ T-cell responses. By using highly purified neutrophils from peritoneal exudates and bone marrow, we have shown that neutrophils cross-present ovalbumin to a CD8+ T-cell hybridoma and to naive CD8+ T cells from OT1 transgenic mice. Cross-presentation by neutrophils was TAP and proteasome dependent and was as efficient as in macrophages. Moreover, it actually occurred earlier than in professional antigen-presenting cells. Peritoneal exudate neutrophils from mice injected intraperitoneally with ovalbumin also cross-presented ovalbumin, proving that neutrophils take up and present exogenous antigens into major histocompatibility complex I (MHC I) molecules in vivo. We then evaluated the in vivo influence of antigen cross-presentation by neutrophils on CD8+ T-cell response using beta2-microglobulin-deficient mice transferred with OT1 CD8+ T cells and injected with ovalbumin-pulsed neutrophils. Four days after neutrophil injection, OT1 cells proliferated and expressed effector functions (IFN-gamma production and cytolysis). They also responded efficiently to a rechallenge with ovalbumin-pulsed dendritic cells in CFA. These data are the first demonstration that neutrophils cross-prime CD8+ T cells in vivo and suggest that they may constitute, together with professional antigen-presenting cells, an attractive target to induce cytotoxic T cells in vaccines.
Beauvillain
Céline
C
Institut National de la Santé et de la Recherche Médicale, U564, University Hospital of Angers, CHU Angers, Immunology and Allergology Laboratory, Angers, France.
Delneste
Yves
Y
Scotet
Mari
M
Peres
Audrey
A
Gascan
Hugues
H
Guermonprez
Pierre
P
Barnaba
Vincenzo
V
Jeannin
Pascale
P
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001202:Ascitic Fluid / Q000166:cytology; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045142:Cross-Priming / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; C477327:transporter associated with antigen processing (TAP); D010047:Ovalbumin; D046988:Proteasome Endopeptidase Complex