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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2965-2973. Prepublished online as a Blood First Edition Paper on June 11, 2007; DOI 10.1182/blood-2006-12-063826.
IMMUNOBIOLOGY Neutrophils efficiently cross-prime naive T cells in vivo1 Institut National de la Santé et de la Recherche Médicale (INSERM), U564, University Hospital of Angers, CHU Angers, Immunology and Allergology Laboratory, Angers, France; 2 INSERM, U564, University of Angers, Angers, France; 3 Institut Curie, INSERM, U653, Paris, France; and 4 Istituto Pasteur-Cenci Bolognetti, Università degli Studi di Roma La Sapienza, Rome, Italy
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 ß2-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-
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
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. 