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 1) molecules in vivo. We then evaluated the in vivo influence of antigen cross presentation by neutrophils on CD8(+) T-cell response using beta 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-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.