A Novel NKR-P1Bbright NK Cell Subset Expresses an Activated CD25+CX3CR1+CD62L−CD11b−CD27− Phenotype and Is Prevalent in Blood, Liver, and Gut-Associated Lymphoid Organs of Rats

Inngjerdingen, Marit; Kveberg, Lise; Vaage, John T.

doi:10.4049/jimmunol.1003939

Cited by 15 publications

(17 citation statements)

References 49 publications

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“…This pattern is suggestive of subsets differentially regulated by MHC-I-dependent and MHC-I-independent recognition mechanisms. In addition, further characterization has revealed Nkrp1b to be highly expressed by unique subset(s) of circulating and liver/gut-resident lymphocytes, some of which may include mature/activated NK cells and/or ILC-like cells; these cells are enriched for CD8α, CD25, CD93, CX 3 CR1, but depleted for CD62L, CD27, and CD11b (90). Interestingly, Nkrp1g transcripts are exclusively expressed in the Ly49s3 + subset, while Nkrp1f is expressed in both subsets (22).…”

Section: Expressionmentioning

confidence: 99%

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

Kirkham

Carlyle

2014

Front. Immunol.

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The NKR-P1 receptors were identified as prototypical natural killer (NK) cell surface antigens and later shown to be conserved from rodents to humans on NK cells and subsets of T cells. C-type lectin-like in nature, they were originally shown to be capable of activating NK cell function and to recognize ligands on tumor cells. However, certain family members have subsequently been shown to be capable of inhibiting NK cell activity, and to recognize proteins encoded by a family of genetically linked C-type lectin-related ligands. Some of these ligands are expressed by normal, healthy cells, and modulated during transformation, infection, and cellular stress, while other ligands are upregulated during the immune response and during pathological circumstances. Here, we discuss historical and recent developments in NKR-P1 biology that demonstrate this NK receptor–ligand system to be far more complex and diverse than originally anticipated.

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Section: Expressionmentioning

confidence: 99%

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

Kirkham

Carlyle

2014

Front. Immunol.

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“…We previously identified a subset of rat NK cells lacking expression of both NKR-P1B and Ly49 receptors. That subset is present in all tissues, and we showed that, in the blood, the subset was hyporesponsive in terms of IFN-g production and cytotoxicity [22]. Here, we have characterized that subset further and show that its functional capacity is linked to induced expression of NKR-P1B.…”

Section: Introductionmentioning

confidence: 66%

“…1E). The discrepancy between the degranulation and cytotoxicity assays for the Ly49s3 + subset was unexpected because we previously showed similar levels of perforin and granzyme B and the cytotoxic ability of blood-derived Ly49s3 + and NKR-P1B + subsets [22].…”

Section: Nkr-p1b 2 Ly49s3 2 Nk Cells Are Hyporesponsivementioning

confidence: 86%

“…Possibly, the NKR-P1B + cells that develop from NKR-P1B 2 Ly49s3 2 NK cells are retained in certain tissues, such as the spleen. We have previously shown that a subset of NK cells expressing a NKR-P1B bright phenotype was preferentially found in certain tissues, such as the blood, liver, Peyer's patches, mesenteric lymph nodes, and thymus [22]. Possibly, the tissue microenvironment has an important role for migration to, or retention of, the newly expressing NKR-P1B cells within the spleen.…”

Section: Discussionmentioning

confidence: 99%

“…Rat NK cells consist of 2 major, fully functional subsets expressing either Ly49s3 or NKR-P1B. We previously observed a small subset lacking expression of both NKR-P1B and Ly49s3 in all tested tissues, and decreased IFN-g production and cytotoxicity by blood NKR-P1B 2 Ly49s3 2 NK cells compared with the 2 other NK cell subsets [22]. Here, we recapitulated those findings, showing lower IFN-g production from splenic NKR-P1B 2 Ly49s3 2 NK cells after overnight stimulation with a cocktail of IL-2, IL-12, IL-15, and IL-18 as compared with the NKR-P1B + and Ly49s3 + singlepositive subsets (Fig.…”

Section: Nkr-p1b 2 Ly49s3 2 Nk Cells Are Hyporesponsivementioning

confidence: 94%

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Frontline Science: A hyporesponsive subset of rat NK cells negative for Ly49s3 and NKR-P1B are precursors to the functionally mature NKR-P1B+ subset

Sudworth

Vaage

Inngjerdingen

et al. 2017

Journal of Leukocyte Biology

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Rat NK cells are divided into major subsets expressing either Ly49 receptors or the inhibitory NKR-P1B receptor in conjunction with NKG2A/C/E receptors. A minor subset of NKp46 cells lacking expression of both Ly49 receptors and NKR-P1B is present in blood and spleen and is associated with decreased functional competence. We hypothesized that this subset may represent precursors to Ly49 and/or NKR-P1B NK cells. When cultured in vitro in IL-2 and IL-15 or adoptively transferred to syngeneic hosts, a portion of NKR-P1BLy49s3 cells transformed to express NKR-P1B, but very little Ly49s3. Acquisition of NKR-P1B by NKR-P1BLy49s3 cells coincided with increased degranulation. In addition, although NKR-P1BLy49s3 cells highly proliferate, proliferative activity was reduced upon acquisition of NKR-P1B at comparable levels to bona fide NKR-P1B NK cells. A fraction of NKR-P1BLy49s3 cells remained negative for NKR-P1B, both in vitro and after adoptive transfer in vivo. Most NKR-P1BLy49s3 cells expressed the transcription factor Eomesodermin and NK cell markers, indicating that these cells represent conventional NK cells. Our findings suggest that the NKR-P1BLy49s3 NK cells are precursors to NKR-P1B single-positive cells and that functional competence is acquired upon expression of NKR-P1B.

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Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

et al. 2014

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Natural killer cell receptor protein 1 (NKR-P1) molecules are C-type lectin-like receptors modulating cellular responses toward target cells expressing C-type lectin-like related (Clr) molecules. Although the function of the prototypic rat NKR-P1A receptor and its inhibitory counterpart NKR-P1B are known, little is known about NKR-P1F and NKR-P1G apart from their promiscuity for Clr ligands. Here we generated mAbs against both receptors for phenotypic and functional analyses in rat tissues. NKR-P1F induced redirected lysis and robust Ca 2+ signaling in NK cells, which were prevented by simultaneous engagement of NKR-P1G. NKR-P1G also inhibited NK-cell lysis of Clr transfectants. NKR-P1F was expressed by most NK cells and NKR-P1A + T cells in all tissues analyzed, and by many NKR-P1A − intestinal T cells, while NKR-P1G was expressed by subsets of these cells with highest prevalence in gut and liver. In the intraepithelial compartment, the proportion of NKR-P1A + and NKR-P1F + cells was high at birth and thereafter declined, while NKR-P1B + and NKR-P1G + cells increased with age. Expression levels were also modulated by cytokines, with an increase of NKR-P1B and NKR-P1G induced by inflammatory cytokines, and a reduction of NKR-P1A by TGF-β. The physiological impact of NKR-P1 receptors might thus be dependent on age, tissue, and inflammatory status.Keywords: C-type lectin-related molecules r NK-cell receptors r NKR-P1 r Rodent Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNatural killer (NK) cells are innate lymphoid cells with the ability to eliminate virally infected cells and transformed or allogeneic cells. They produce cytokines early in the immune response, and play an important role in shaping the immune response, e.g. in the context of inflammation and transplantation. These tasks are controlled by a wide range of receptors with different functions and ligands, such as Ly49 receptors, which recognize both classical and nonclassical MHC class I molecules, as well as MHC Correspondence: Dr. Lise Kveberg e-mail: lise.kveberg@rr-research.no class I-like virally encoded ligands [1][2][3]. Another family of MHCbinding receptors is the conserved NKG2/CD94 heterodimers, which bind the nonclassical MHC molecule HLA-E in human [4], its rodent homologue Qa-1 b in the mouse [5,6] and RT.BM1 in the rat [7]. Both the Ly49 and NKG2/CD94 receptor families contain inhibitory and activating members. NKG2D is a promiscuous activating receptor, recognizing several MHC class I-related ligands frequently upregulated upon cellular stress and associated with viral infection and malignant transformation [8].The activating NK cytotoxicity receptors react with several virus-derived and endogenous ligands [9,10].One of the earliest NK-cell receptors to be characterized was the NK-cell receptor protein 1A (NKR-P1A) in the rat, which is C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 502Lise Kveberg et al. Eur. J. Immunol. 2015. 45: 501-...

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A Novel NKR-P1Bbright NK Cell Subset Expresses an Activated CD25+CX3CR1+CD62L−CD11b−CD27− Phenotype and Is Prevalent in Blood, Liver, and Gut-Associated Lymphoid Organs of Rats

Cited by 15 publications

References 49 publications

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

Frontline Science: A hyporesponsive subset of rat NK cells negative for Ly49s3 and NKR-P1B are precursors to the functionally mature NKR-P1B+ subset

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

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