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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.
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Submitted December 19, 2006
Accepted June 7, 2007
Neutrophils efficiently cross-prime naive T cells in vivo
Celine Beauvillain, Yves Delneste, Mari Scotet, Audrey Peres, Hugues Gascan, Pierre Guermonprez, Vincenzo Barnaba, and Pascale Jeannin*
U564, University Hospital of Angers; INSERM, Angers, France
Institut Curie, U653, INSERM, Paris, France
Istituto Pasteur-Cenci Bolognetti, Universita degli Studi di Roma "La Sapienza", Roma, Italy
* Corresponding author; email: pascale.jeannin{at}univ-angers.fr.
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 MHC-I molecules in vivo. We then evaluated the in vivo influence of antigen cross-presentation by neutrophils on CD8+ T-cell response using  2-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 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.
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