NK cell lines of different maturational status can be obtained from mouse foetal liver

Manoussaka, Maria; Georgiou, Andrew; Rossiter, Beth; Shrestha, Sunil; Toomey, Jennifer A.; Sivakumar, Pallavur V.; Bennett, Michael J.; Kumar, Vinay; Brooks, Colin G.

doi:10.1042/bst025174s

Cited by 15 publications

(19 citation statements)

References 1 publication

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“…Our findings suggest that 2B4:SHIP signaling could also play a role in early NK development to promote the efficient acquisition of NK receptors that sense MHC-I ligands. In fact, expression of 2B4 (27,28) and SHIP precedes expression of the Ly49 and CD94/NKG2 receptors in NK development. The early expression of 2B4 in developing NK cells may be necessary to achieve self-tolerance until a properly diverse Ly49 and CD94/NKG2 repertoire is acquired.…”

Section: Discussionmentioning

confidence: 99%

SHIP Influences Signals from CD48 and MHC Class I Ligands That Regulate NK Cell Homeostasis, Effector Function, and Repertoire Formation

Fortenbery

Paraiso

Taniguchi

et al. 2010

The Journal of Immunology

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Previously, we showed that 2B4 is a dominant inhibitory receptor in SHIP-deficient NK cells that prevents efficient cytolysis of complex targets. We show in this study that 2B4 deficiency restores homeostatic control and cytolytic function to SHIP-deficient NK cells. However, 2B4−/−SHIP−/− NK cells still exhibit a profound disruption of their NK receptor repertoire and are compromised for induction of IFN-γ by several NK-activating receptors, including NKp46, NK.1.1, and NKG2D. In addition, we find that 2B4−/− NK cells have an extensively disrupted repertoire, including a supernormal frequency of NKp46+ NK cells. Consequently IFN-γ is induced on a much higher percentage of 2B4−/− NK cells following engagement of NKp46. We also find that both SHIP and 2B4 are required to prevent expression of Ly49B, a myeloid lineage MHC class I receptor not normally expressed by the NK lineage. Finally, when SHIP-deficient NK cells are on an H-2d background, they exhibit supernormal levels of Ly49A and possess normal cytolytic function against MHC-matched tumor targets and enhanced cytolysis of MHC mismatched tumor targets. However, despite normal or elevated cytolytic function, H2d SHIP−/− NK cells exhibit poor induction of IFN-γ like their H2b+ or 2B4−/− counterparts, demonstrating a uniform requirement for SHIP in induction of IFN-γ downstream of key NK activating receptors. These findings reveal a complex interplay of SHIP, 2B4, and MHC in the regulation of homeostasis, effector function, and repertoire formation in the NK cell lineage.

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Section: Discussionmentioning

confidence: 99%

SHIP Influences Signals from CD48 and MHC Class I Ligands That Regulate NK Cell Homeostasis, Effector Function, and Repertoire Formation

Fortenbery

Paraiso

Taniguchi

et al. 2010

The Journal of Immunology

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“…Studying the interaction of these cells with target cells bearing Qa1 molecules is complicated by the fact that Qa1 receptor-expressing (Qa1R ϩ ) adult NK cells also express a variable selection of Ly49 receptors that can deliver inhibitory (or activatory) signals after interaction with classical class I molecules (7,8,15). To avoid this problem we have taken advantage of the fact that fetal NK cells are deficient in the expression of Ly49 receptors (16), lack detectable receptors for classical class I molecules (17), yet express CD94/ NKG2 receptors for Qa1 (17,18). These latter receptors are acquired in a stochastic manner during the development of fetal NK cells in vitro (17), allowing the selection of clones or lines that are composed predominantly of Qa1R Ϫ or Qa1R ϩ cells.…”

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confidence: 99%

Functional Analysis of the Molecular Factors Controlling Qa1-Mediated Protection of Target Cells from NK Lysis

Gays

Fraser

Toomey

et al. 2001

The Journal of Immunology

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CD94/NKG2 receptors on mouse NK cells recognize the nonclassical class I molecule Qa1 and can deliver inhibitory signals that prevent NK cells from lysing Qa1-expressing cells. However, the exact circumstances under which Qa1 protects cells from NK lysis and, in particular, the role of the dominant Qa1-associated peptide, Qdm, are unclear. In this study, we examined in detail the lysis of Qa1-expressing cells by fetal NK cells that express CD94/NKG2 receptors for Qa1 but that lack receptors for classical class I molecules. Whereas mouse L cells and human C1R cells transfected with Qa1 were resistant to lysis by these effectors, Qa1-transfected TAP-deficient human T2 cells showed no resistance despite expressing high levels of surface Qa1. However, these cells could be efficiently protected by exposure to low concentrations of Qdm peptide or certain Qdm-related peptides. By contrast, even prolonged exposure of TAP-deficient RMA/S cells to high doses of Qdm peptide failed to induce levels of surface Qa1 detectable with a Qa1-specific mAb or to protect them from NK lysis, although such treatment induced sensitivity to lysis by Qa1-specific CTL. Collectively, these findings indicate that high surface expression of Qa1 is necessary but not sufficient for protection, and that effective protection requires the expression of sufficient levels of suitable Qa1-peptide complexes to overcome activatory signals. Results obtained with a series of substituted Qdm peptides suggest that residues at positions 3, 4, 5, and 8 of the Qdm sequence, AMAPRTLLL, are important for recognition of Qa1-Qdm complexes by inhibitory CD94/NKG2 receptors.

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“…This explanation is incomplete, however, as the differences in chimerism were clearly evident even at the 3 week time point in our cohort. Ly49-negative fetal NK cells can respond to class I antigens and may also function as an immunologic barrier to allogeneic transplantation in the early gestational fetus [19][20][21][22].…”

Section: Discussionmentioning

confidence: 99%

Donor major histocompatibility complex class I expression determines the outcome of prenatal transplantation

Durkin¹,

Jones²,

Elnaggar³

et al. 2008

Journal of Pediatric Surgery

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NK cell lines of different maturational status can be obtained from mouse foetal liver

Cited by 15 publications

References 1 publication

SHIP Influences Signals from CD48 and MHC Class I Ligands That Regulate NK Cell Homeostasis, Effector Function, and Repertoire Formation

SHIP Influences Signals from CD48 and MHC Class I Ligands That Regulate NK Cell Homeostasis, Effector Function, and Repertoire Formation

Functional Analysis of the Molecular Factors Controlling Qa1-Mediated Protection of Target Cells from NK Lysis

Donor major histocompatibility complex class I expression determines the outcome of prenatal transplantation

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