Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming.
Naive T cells are stimulated by antigen-presenting dendritic cells (DCs) in secondary lymphoid organs, but whether other types of cell participate in T cell priming is unclear. Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs. Recruitment of NK cells is also induced by some, but not all, adjuvants and correlates with the induction of T helper cell type 1 (T(H)1) responses. NK cell depletion and reconstitution experiments show that NK cells provide an early source of interferon-gamma (IFN-gamma) that is necessary for T(H)1 polarization. Taken together, our results identify an induced pathway of NK cell migration in antigen-stimulated lymph nodes and a mechanism by which some adjuvants may facilitate T(H)1 responses.
Martín-Fontecha
Alfonso
A
Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
Thomsen
Lindy L
LL
Brett
Sara
S
Gerard
Craig
C
Lipp
Martin
M
Lanzavecchia
Antonio
A
Sallusto
Federica
F
D000276:Adjuvants, Immunologic; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
D000276:Adjuvants, Immunologic; C515371:Ccr7 protein, mouse; C515188:Cxcr3 protein, mouse; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma