Ovine CD16<sup>+</sup>/CD14<sup>-</sup>blood lymphocytes present all the major characteristics of natural killer cells

Elhmouzi-Younes, Jamila; Boysen, Preben; Pende, Daniela; Storset, Anne K.; Vern, Yves Le; Laurent, Fabrice; Drouet, Françoise

doi:10.1051/vetres/2009052

Cited by 20 publications

(27 citation statements)

References 44 publications

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“…Secondly, approximately 80-90% of the NKp46 + cells expressed CD16 (FcγRIII) - the receptor that mediates antibody-dependent cell-mediated cytotoxicity by NK cells - comparable to levels observed in the equivalent populations in cattle and in human PBMC [34,36]. These data indicate that the CD16 + /CD14 - phenotype used recently by Elhmouzi-Younes et al [21] to define peripheral ovine NK cells successfully identifies most but not all NKp46 + cells and could be equally well applied to NK cells in secondary lymphoid tissues. Thirdly, ovine NKp46 + cells expressed perforin, an integral part of the granule exocytosis mediated cytotoxicity machinery used by NK cells for target cell lysis.…”

Section: Discussionsupporting

confidence: 70%

NKp46 defines ovine cells that have characteristics corresponding to NK cells

Connelley

Storset

Pemberton

et al. 2011

Vet Res

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Natural killer (NK) cells are well recognized as playing a key role in innate immune defence through cytokine production and cytotoxic activity; additionally recent studies have identified several novel NK cell functions. The ability to study NK cells in the sheep has been restricted due to a lack of specific reagents. We report the generation of a monoclonal antibody specific for ovine NKp46, a receptor which in a number of mammals is expressed exclusively in NK cells. Ovine NKp46+ cells represent a population that is distinct from CD4+ and γδ+ T-cells, B-cells and cells of the monocytic lineage. The NKp46+ cells are heterogenous with respect to expression of CD2 and CD8 and most, but not all, express CD16 - characteristics consistent with NK cell populations in other species. We demonstrate that in addition to populations in peripheral blood and secondary lymphoid organs, ovine NKp46+ populations are also situated at the mucosal surfaces of the lung, gastro-intestinal tract and non-gravid uterus. Furthermore, we show that purified ovine NKp46+ populations cultured in IL-2 and IL-15 have cytotoxic activity that could be enhanced by ligation of NKp46 in re-directed lysis assays. Therefore we conclude that ovine NKp46+ cells represent a population that by phenotype, tissue distribution and function correspond to NK cells and that NKp46 is an activating receptor in sheep as in other species.

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Section: Discussionsupporting

confidence: 70%

NKp46 defines ovine cells that have characteristics corresponding to NK cells

Connelley

Storset

Pemberton

et al. 2011

Vet Res

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“…CD16 expression on sheep PBMC is reported at a median 9.1% (7.5-12.6) and 10.2% (8.1-11) for cows, in a pattern similar to Fig. 3A (Elhmouzi-Younes et al, 2010). To compare our data in context, the percent of labeled equine PBMC was calculated by gating only the mAb 9G5-labelled monocyte and lymphocyte populations, yielding a median 3.7% (1.1-8.1).…”

Section: Discussionsupporting

confidence: 64%

“…In humans, cows, and sheep, a substantial fraction of CD16 + monocytes are positive for the LPS receptor CD14 (Elhmouzi-Younes et al, 2010; Ziegler-Heitbrock, 2007). To determine whether this is also the case in the horse, leukocytes from 6 horses were labeled with mAb 9G5 and a monoclonal antibody to CD14.…”

Section: Resultsmentioning

confidence: 99%

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Generation and characterization of monoclonal antibodies to equine CD16

Noronha

Harman

Wagner

et al. 2012

Veterinary Immunology and Immunopathology

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The low-affinity Fc receptor CD16 plays a central role in the inflammatory and innate immune responses of many species, but has not yet been investigated in the horse. Using the predicted extracellular region of equine CD16 expressed as a recombinant fusion protein with equine IL-4 (rIL-4/CD16), we generated a panel of mouse monoclonal antibodies (mAbs) that recognize equine CD16. Nine mAbs were chosen for characterization based upon recognition of CD16, but not IL-4, in ELISA. All nine mAbs recognized full-length, cell-surface CD16 expressed as a GFP fusion protein by CHO cells, but not the closely related Fc receptor CD32 expressed in the same system. In flow cytometric analysis with equine peripheral leukocytes, the mAbs labeled cells in the granulocyte, monocyte, and lymphocyte populations in a pattern consistent with other species. Monocytes that were strongly labeled with CD16 mAb 9G5 were also positive for the LPS receptor CD14. Cytospins made with peripheral leukocytes were immunohistochemically labeled and showed mAb recognition of primarily mononuclear cells. ELISA revealed that the nine mAbs can be grouped into three patterns of epitope recognition. These new antibodies will serve as useful tools in the investigation of equine immune responses and inflammatory processes.

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“…Up to now, the immune responses of ruminant NK cells in responses to PPRV infection were limited. Ovine CD16 + CD14 − lymphocyte displays the phenotype and functional characteristics of NK cells (21), which provide some insight into ruminant NK cell biology. Various cytokines can modulate NK cell function, including interleukin (IL)-12, interferon (IFN)-α, interleukin (IL)-21, and transforming growth factor (TGF)-β (22).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1 Negatively Regulates Peripheral NK Cell Function via Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Signaling Pathways During PPRV Infection

et al. 2020

Front. Immunol.

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Peste des petits ruminants virus (PPRV) has emerged as a significant threat to the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and induces in the hosts a transient but severe immunosuppression, especially innate immunity. However, it remains largely unknown how NK cells respond and are regulated at the earliest time points after an acute viral PPRV infection in goats. In this study, we revealed that multiple immune responses of goat peripheral NK cells were compromised during PPRV infection, including the cytolytic effector molecule expression and cytokine production. Importantly, we demonstrated that PPRV infection stimulated the expression of TWEAK, a negative regulator of cytotoxic function of NK cells, which may be involved in the suppression of cytotoxicity as well as cytokine production in infected goat NK cells. Furthermore, we found that PPRV infection induced TWEAK expression in goat NK cells involving post-transcription by suppressing miR-1, a novel negative miRNA directly targeting the TWEAK gene. Moreover, replication of virus is required for inhibition of miR-1 expression during PPRV infection, and the non-structural V protein of PPRV plays an important role in miR-1 mediated TWEAK upregulation. Additionally, we revealed that the regulation of NK cell immune responses by TWEAK is mediated by MyD88, SOCS1, and STAT3. Taken together, our results demonstrated that TWEAK may play a key role in regulating goat peripheral NK cell cytotoxicity and cytokine expression levels during PPRV infection.

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Ovine CD16⁺/CD14^-blood lymphocytes present all the major characteristics of natural killer cells

Cited by 20 publications

References 44 publications

NKp46 defines ovine cells that have characteristics corresponding to NK cells

NKp46 defines ovine cells that have characteristics corresponding to NK cells

Generation and characterization of monoclonal antibodies to equine CD16

MicroRNA-1 Negatively Regulates Peripheral NK Cell Function via Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Signaling Pathways During PPRV Infection

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Ovine CD16+/CD14-blood lymphocytes present all the major characteristics of natural killer cells

Cited by 20 publications

References 44 publications

NKp46 defines ovine cells that have characteristics corresponding to NK cells

NKp46 defines ovine cells that have characteristics corresponding to NK cells

Generation and characterization of monoclonal antibodies to equine CD16

MicroRNA-1 Negatively Regulates Peripheral NK Cell Function via Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Signaling Pathways During PPRV Infection

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Ovine CD16⁺/CD14^-blood lymphocytes present all the major characteristics of natural killer cells