Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction

Spaggiari, Grazia Maria; Contini, Paola; Dondero, Alessandra; Carosio, Roberta; Puppo, Francesco; Indiveri, Francesco; Zocchi, Maria Raffaella; Poggi, Alessandro

doi:10.1182/blood-2002-04-1284

Cited by 91 publications

(122 citation statements)

References 53 publications

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“…17 The addition of low concentrations of IL-2 (20 ng/ml) to the culture medium significantly increased the numbers of NK cells stimulated with 4 or 8 mg of iMICA protein for 3 or 5 days (Figure 2a). Previous reports have shown that soluble HLA class I molecules induce the apoptosis of NK cells through the engagement of CD8 22 or killing immunoglobulin-like receptors (KIR) 23 Because of the similarities between the a3 domains of classical HLA I molecules and MICA proteins, we investigated whether iMICA could promote the apoptosis of NK cells. As observed with ib2m, iMICA had no impact on the apoptosis of NK cells after 3 or 5 days of stimulation (Figure 2b).…”

Section: Mica Synergizes With Ilmentioning

confidence: 99%

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Gong

Xiao

et al. 2010

Cell Mol Immunol

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Major histocompatibility complex (MHC) class I chain-related protein A (MICA), which is a ligand for human NKG2D, is expressed by a variety of epithelial tumor cells and promotes the activation of natural killer (NK), CD8 1 and cd-T cells. Although ectopic expression of MICA on tumor cells elicits anti-tumor responses, soluble MICA downregulates the activities of lymphocytes. In this study, we showed that recombinant, immobilized MICA (iMICA) molecules coated on plastic wells weakly promote peripheral NK cell activation, secretion of interferon (IFN)-c and degranulation without inducing apoptosis. In addition, iMICA synergized with IL-15 and soluble 4-1BB ligand (s4-1BBL) to expand NK cells 25-to 42-fold in a 13-day culture, whereas NK cells stimulated only with IL-15 and s4-1BBL expanded 10-to 16-fold. In contrast to NK cells expanded by IL-15 and s4-1BBL stimulation, NK cells expanded long term in the presence of iMICA exhibited increased cytotoxicity against leukemia cells. These results suggest that large numbers of NK cells with high cytotoxicity can be generated by stimulation with IL-15 and s4-1BBL in the presence of iMICA and that these cells can be used for adoptive cancer immunotherapy. Studies on the 4-1BB signaling pathway have shown that ligation of 4-1BB promotes the survival and multiplication of CD8 1 T and NK cells. 6 IL-15 is essential for the development and function of NK cells. 7 Coculture of NK cells with K562 cells ectopically coexpressing 4-1BB ligand (4-1BBL) and membrane-bound IL-15 effectively promotes the expansion of NK cells in vitro and mediates their cytotoxicity against some leukemia cells. 8,9 In addition, IL-15 upregulates the expression of NKG2D on NK and T cells, even in the presence of soluble NKG2DL. 10 IL-15 and NKG2D signals cross-regulate each other and

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Section: Mica Synergizes With Ilmentioning

confidence: 99%

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Gong

Xiao

et al. 2010

Cell Mol Immunol

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“…We have demonstrated recently that NK cell triggering via HLA-I receptors, including CD8 Ag and the activating isoforms of inhibitory receptor superfamily (IRS) members, induces FasL release, which in turn leads to NK cell death (15,16). This finding would suggest that, not only FasL from tumor cells (13), but also FasL produced and released by NK cells can induce NK cell death.…”

mentioning

confidence: 92%

“…Under these culture conditions, by day 15 all cells expressed CD16 and CD56 Ags. CD3 Ϫ CD16 ϩ clones were obtained by culturing highly purified CD3 Ϫ NK cells under limiting dilution conditions, as previously reported (16). In particular, decreasing number of NK cells (100, 50, 25, 12, and 6) was seeded in 200 l/well in 96-well plates.…”

Section: Isolation and Culture Of Polyclonal And Clonal Nk Cell Populmentioning

confidence: 99%

“…The resulting cell population was 50 -70% CD16 ϩ (range of eight different experiments), but 99% CD3 Ϫ . Highly purified CD3 Ϫ cells were stimulated with 10 g/ml PHA and cultured in 96-well U-bottom microplates (Greiner Labortechnic) with RPMI 1640 medium supplemented with 10% FCS in the presence of 100 U/ml rIL-2 in a final volume of 200 l/well in the presence of 10 5 /well irradiated allogeneic PBMC and 10 4 /well 721.221 lymphoblastoid cell line (16). Under these culture conditions, by day 15 all cells expressed CD16 and CD56 Ags.…”

Section: Isolation and Culture Of Polyclonal And Clonal Nk Cell Populmentioning

confidence: 99%

“…Single fluorescence staining was performed, as described elsewhere (16,17). Briefly, aliquots of 10 5 cells were stained with the corresponding mAb, followed by PE-conjugated anti-isotype-specific GAM serum (Southern Biotechnology Associates), or with an unrelated mAb (BD Biosciences), followed by the fluorescent second reagent.…”

Section: Indirect Immunofluorescencementioning

confidence: 99%

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Tumor-Induced Apoptosis of Human IL-2-Activated NK Cells: Role of Natural Cytotoxicity Receptors

Poggi¹,

Massaro

Negrini

et al. 2005

The Journal of Immunology

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We provide evidence that tumor cells can induce apoptosis of NK cells by engaging the natural cytotoxicity receptors (NCR) NKp30, NKp44, and NKp46. Indeed, the binding between NCR on NK cells and their putative ligands on tumor target cells led to NK cell apoptosis, and this event was abolished by blocking NCR/NCR-ligand interaction by anti-NCR-specific mAbs. The engagement of NCR induced up-regulation of Fas ligand (FasL) mRNA, FasL protein synthesis, and release. In turn, FasL interacting with Fas at NK cell surface causes NK cell suicide, as apoptosis of NK cells was inhibited by blocking FasL/Fas interaction with specific mAbs. Interestingly, NK cell apoptosis, but not killing of tumor target cells, is inhibited by cyclosporin A, suggesting that apoptosis and cytolysis are regulated by different biochemical pathways. These findings indicate that NCR are not only triggering molecules essential for antitumor activity, but also surface receptors involved in NK cell suicide.

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Association of killer cell immunoglobulin‐like receptors with scleroderma

Momot

Koch

Hunzelmann

et al. 2004

Arthritis & Rheumatism

133

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Objective. Scleroderma is an autoimmune disorder of unknown etiology. A genetic contribution has been demonstrated, and genes influencing activation of the immune system have been potentially identified as candidate genes in this process. The repertoire of killer cell immunoglobulin-like receptors (KIRs) that are involved in the activation of T cells and natural killer cells is highly variable. Recently, an association of KIR2DS2 with vasculitis in patients with rheumatoid arthritis has been reported. Because scleroderma is characterized by an involvement of the vascular system, we sought to determine whether KIR2DS2 is associated with scleroderma.Methods. We typed 9 KIR genes in 102 patients with scleroderma and in 100 blood donors, using polymerase chain reaction on genomic DNA.Results. Twelve patients with scleroderma, compared with only 2 blood donors, had KIR phenotypes characterized by the presence of the activating KIR2DS2 and the absence of the corresponding inactivating KIR2DL2 (P ‫؍‬ 0.005).Conclusion. The genetic combination of KIR2DS2؉ and KIR2DL2؊ is associated with scleroderma.

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Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction

Cited by 91 publications

References 53 publications

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Tumor-Induced Apoptosis of Human IL-2-Activated NK Cells: Role of Natural Cytotoxicity Receptors

Association of killer cell immunoglobulin‐like receptors with scleroderma

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