Neutrophils efficiently cross-prime naive T cells in vivo
Neutrophils efficiently cross-prime naive T cells in vivo
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DOI：
10.1182/blood-2006-12-063826
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发表时间：
2007-10-15
期刊：
影响因子：
20.3
通讯作者：
Jeannin, Pascale
中科院分区：
文献类型：
--
作者：
Beauvillain, Celine;Delneste, Yves;Jeannin, Pascale
中性粒细胞是专业的吞噬细胞，早期大量迁移到感染部位。我们的研究分析了中性粒细胞如何交叉呈递抗原并影响CD8(+)T细胞反应。通过从腹膜渗出液和骨髓中提取高纯度的中性粒细胞，我们发现中性粒细胞将卵清蛋白传递给CD8+T细胞杂交瘤和来自OT1转基因小鼠的幼稚CD8+T细胞。中性粒细胞的交叉递呈依赖于TAP和蛋白酶体，并且与巨噬细胞一样有效。此外，它实际上比专业的抗原提呈细胞发生得更早。注射卵白蛋白的小鼠腹膜渗出液中的中性粒细胞也交叉呈递卵白蛋白，证明中性粒细胞在体内摄取并将外源性抗原呈递到主要组织相容性复合体I(MHC 1)分子中。然后，我们通过将OT1 CD8+T细胞转移到β2-微球蛋白缺陷小鼠体内，并注射卵蛋白冲击的中性粒细胞，评估了中性粒细胞的抗原交叉提呈对CD8(+)T细胞反应的影响。注射中性粒细胞4天后，OT1细胞增殖并表达效应功能(产生干扰素-γ和溶解细胞)。在CFA中，他们还用卵清蛋白冲击的树突状细胞有效地应对了重新挑战。这些数据是首次证明中性粒细胞在体内交叉激发CD8(+)T细胞，并表明它们可能与专业的抗原提呈细胞一起构成诱人的靶点，在疫苗中诱导细胞毒性T细胞。
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.