Primed Antigen-Specific CD4+ T Cells Are Required for NK Cell Activation In Vivo upon Leishmania major Infection

被引:63
作者
Bihl, Franck
Pecheur, Julien
Breart, Beatrice
Poupon, Gwenola
Cazareth, Julie
Julia, Valerie [2 ]
Glaichenhaus, Nicolas [2 ]
Braud, Veronique M. [1 ]
机构
[1] Univ Nice Sophia Antipolis, Inst Pharmacol Mol & Cellulaire, CNRS, Unite Mixte Rech 6097, F-06560 Valbonne, France
[2] Univ Nice Sophia Antipolis, Inst Natl Rech Sci Sante, Inst Pharmacol Mol & Cellulaire, U924, F-06560 Valbonne, France
关键词
NATURAL-KILLER-CELLS; DOUBLE-STRANDED-RNA; DENDRITIC CELLS; IFN-GAMMA; INTERFERON-GAMMA; TUMOR REJECTION; LYMPH-NODES; CROSS-TALK; CUTANEOUS LEISHMANIASIS; VISCERAL LEISHMANIASIS;
D O I
10.4049/jimmunol.1001486
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The ability of NK cells to rapidly produce IFN-gamma is an important innate mechanism of resistance to many pathogens including Leishmania major. Molecular and cellular components involved in NK cell activation in vivo are still poorly defined, although a central role for dendritic cells has been described. In this study, we demonstrate that Ag-specific CD4(+) T cells are required to initiate NK cell activation early on in draining lymph nodes of L. major-infected mice. We show that early IFN-gamma secretion by NK cells is controlled by IL-2 and IL-12 and is dependent on CD40/CD40L interaction. These findings suggest that newly primed Ag-specific CD4(+) T cells could directly activate NK cells through the secretion of IL-2 but also indirectly through the regulation of IL-12 secretion by dendritic cells. Our results reveal an unappreciated role for Ag-specific CD4(+) T cells in the initiation of NK cell activation in vivo upon L. major infection and demonstrate bidirectional regulations between innate and adaptive immunity. The Journal of Immunology, 2010, 185: 2174-2181.
引用
收藏
页码:2174 / 2181
页数:8
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