Neutrophils efficiently cross-prime naive T cells in vivo

• Published in: Blood 2007-10, Vol.110 (8), p.2965-2973
• Main Authors: Beauvillain, Céline, Delneste, Yves, Scotet, Mari, Peres, Audrey, Gascan, Hugues, Guermonprez, Pierre, Barnaba, Vincenzo, Jeannin, Pascale
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - immunology; Ascitic Fluid - cytology; ATP-Binding Cassette Transporters - metabolism; Bone Marrow Cells - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cross-Priming - immunology; Flow Cytometry; Humans; Immunology; Life Sciences; Lymphocyte Activation - immunology; Mice; Neutrophils - immunology; Neutrophils - metabolism; Ovalbumin - immunology; Proteasome Endopeptidase Complex - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-12-063826

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 β2-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-γ 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.