Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity

Mandelboim, Ofer; Malik, Pratap; Davis, Daniel M.; Jo, Chang H.; Boyson, Jonathan E.; Strominger, Jack L.

doi:10.1073/pnas.96.10.5640

Cited by 236 publications

(214 citation statements)

References 29 publications

(18 reference statements)

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“…They are known to mediate direct natural cytotoxicity as well as antibody-dependent cellular cytotoxicity (ADCC). The key involvement of CD16 receptors in ADCC has clearly been shown previously by many laboratories; however, its significance in NK cell direct killing is far less known, although tumor cell ligands have previously been identified that bind NK cell CD16 receptors (Mandelboim et al, 1999). By producing key cytokines and chemokines NK cells are known to regulate the functions of other immune cells (Farag & Caligiuri, 2006;Fildes et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Natural killer cells as effectors of selection and differentiation of stem cells: Role in resolution of inflammation

Jewett

Man

Cacalano

et al. 2014

Journal of Immunotoxicology

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Evidence has previously been demonstrated for the role of NK cells in specific elimination of healthy stem cells (e.g. hMSC, hDPSC, hESC, hiPSC) as well as cancer stem cells, but not their differentiated counterparts. There is also a stage-wise susceptibility to NK cell-mediated cytotoxicity in tumors, in which case the poorly-differentiated tumors are lysed much more than moderately-differentiated tumors. Well-differentiated tumors were lysed the least compared to either moderately-or poorly-differentiated tumors. It has also been reported that inhibition of differentiation or reversion of cells to a less-differentiated stage by blocking NF-B or by gene deletion of COX2 significantly augmented NK cell cytotoxicity against both transformed and healthy cells. Additionally, the cytotoxic function of NK cells was severely inhibited against stem cells when they were cultured in the presence of monocytes. Therefore, it is proposed that CD16 + CD56 dim CD69 À NK cells were important for the selection of stem cells, whereas the CD16 dim/À CD56 dim/+ CD69 + anergized NK cells were important for differentiation and eventual regeneration of the tissues and the resolution of inflammation, thus potentially serving as regulatory NK (NK reg ) cells. The concept of 'split anergy' in NK cells and the generation of NK reg cells with regard to contributions to cell differentiation, tissue repair and regeneration and in tumor resistance are discussed in this review.

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Section: Introductionmentioning

confidence: 99%

Natural killer cells as effectors of selection and differentiation of stem cells: Role in resolution of inflammation

Jewett

Man

Cacalano

et al. 2014

Journal of Immunotoxicology

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“…The integrity of purified NCAM-Ig was verified on Western blots, using NCAM-and hIgG 1 -Fc-reactive antibodies, respectively. CD99-Ig cDNA, granted by Dr. O. Mandelboim (Hebrew University, Jerusalem, Israel), 43 was subcloned into a modified pHbAPr-1-neo expression vector 44 and purified from stably transfected A549 cells using protein A-Sepharose beads.…”

Section: Monoclonal Antibodies Soluble Ncam-ig Fusion Proteinmentioning

confidence: 99%

“…The antiEpCAM mAb HEA125, 39 the mAb L1-11A recognizing the ectodomain of human L1 (subclone of UJ 127.11) 35 For the production of NCAM-Ig fusion proteins, a SacIIEco147I fragment coding for amino acids 1-178 of the NCAM ectodomain was excised from IRATp970G0970D and subcloned into the SmaI site of pBluescript KS II1 (Stratagene, Amsterdam, The Netherlands), containing between the BamHI and XbaI sites a cDNA coding for the Fc portion of human IgG 1 . 43 The complete construct was subcloned into the vertebrate expression vector pMT21mcs (a gift of Dr. J. Neefjes, NKI, Amsterdam, The Netherlands). NCAM-Ig fusion protein was purified from the supernatant of transiently transfected 293 cells using protein A-Sepharose beads (Amersham BioSciences, Freiburg, Germany).…”

Section: Monoclonal Antibodies Soluble Ncam-ig Fusion Proteinmentioning

confidence: 99%

Blockade of natural killer cell‐mediated lysis by NCAM140 expressed on tumor cells

Jarahian

Watzl

Issa

et al. 2007

Intl Journal of Cancer

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Expression of the neural cell adhesion molecule (NCAM) on malignant cells of neuroendocrine, epithelial and hematopoeitic origin has been reported, but its role for tumor cell recognition by the immune system remained uncertain so far. We have studied the cytotoxicity of the natural killer (NK) cell line NK92 and polyclonal NK cells from different donors, against NCAM-deficient and NCAM-transfected tumors. While the pancreatic carcinoma PANC-1 and the glioblastoma T98G showed no enhanced susceptibility to NK lysis after NCAM transfection, de novo NCAM expression in HeLa cervical carcinoma, SHEP neuroblastoma and the multiple myeloma lines RPMI-8226 and LP-1 was associated with significantly decreased lysis by NK cells. Binding of an NCAM-specific monoclonal antibody to NCAM-positive target cells was able to reverse the reduced lysis susceptibility. Conjugate formation of NCAM-expressing tumor cells with NK cells was blocked and could be restored by anti-NCAM. NK cell-expressed NCAM molecules which might engage in homotypic cis-or trans-interactions had no apparent inhibitory function. The known cis-ligands of NCAM, heparan sulfate proteoglycan and L1-CAM, were also not directly involved in NK inhibition. ICAM-1 mRNA and cell surface expression was downmodulated in NCAM-transfected HeLa cells. ICAM-1 is involved in killer cell immune synapse formation. Its downmodulation may therefore contribute to the reduced lysis of NCAM-expressing target cells. We conclude that aberrant expression of NCAM on tumor cells of different histogenetic origin can lead to inhibition of target cell recognition and lysis by NK cells. ' 2007 Wiley-Liss, Inc.

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“…Fc␥RIII receptor CD16 is responsible for the antibodydependent cell cytotoxicity (ADCC) mediated by NK cells, but it also mediates cytotoxicity by yet unidentified ligands. 6 Another important activating receptor expressed by NK cells is 2B4/ CD244. 7 This receptor belongs to the CD2 superfamily and is also expressed by all cytolytic lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction

Fauriat

Just-Landi

Mallet

et al. 2006

Blood

320

308

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Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity

Abstract: In

Cited by 236 publications

References 29 publications

Natural killer cells as effectors of selection and differentiation of stem cells: Role in resolution of inflammation

Natural killer cells as effectors of selection and differentiation of stem cells: Role in resolution of inflammation

Blockade of natural killer cell‐mediated lysis by NCAM140 expressed on tumor cells

Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction

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