Abstract
Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46- and NKp46+ cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46high phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α+NKp46- and NKp46+ NK-cell subsets in spleen and blood. Additionally NKp46high NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46high NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46high NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46high NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.
Highlights
Natural Killer (NK) cells were initially characterised by their spontaneous lytic activity against certain tumor and virus-infected cells [1,2]
To expand the knowledge about the phenotype of previously described NKp46-defined NK-cell populations in swine [20], we performed flow cytometric analyses of lymphocytes isolated from spleen and blood
As previously described [20], among CD3- lymphocytes two NK populations could be found in blood, namely NKp46- and NKp46+ cells that were both CD8α+ (Figure 1A, upper graph)
Summary
Natural Killer (NK) cells were initially characterised by their spontaneous lytic activity against certain tumor and virus-infected cells [1,2]. Besides their role as cytotoxic cells through the production of perforin and granzymes, NK cells are potent producers of cytokines like Interferon (IFN)-γ and Tumor Necrosis Factor (TNF)-α [3] and play important roles in immunomodulation and the defence against viral, parasitic and bacterial pathogens [4]. In the mouse likewise CD27 and CD11b (Mac-1) are used to dissect NK cells into functionally and developmentally different subsets [9].
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