MHC-Class I Antigens Regulate Both the Function and the Survival of Human Peripheral Blood NK Cells: Role of Endogenously Secreted TNF-α

Jewett, Anahid; Bonavida, Benjamin

doi:10.1006/clim.2000.4871

Cited by 23 publications

(27 citation statements)

References 28 publications

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“…Previous studies by other groups have also shown that a subset of IL-2 activated NK cells undergo cell death following cross-linking of the CD16 receptor (Ortaldo et al 1995;Azzoni et al 1995). Addition of antibodies to CD56 or LFA-1 did not cause any decrease in NK cell cytotoxicity demonstrating the specificity of CD16 mAb signaling in mediating inhibition of NK cell cytotoxicity (Jewett and Bonavida 2000).…”

Section: Split Anergy In Il-2 Treated Nk Cells Is Induced After Theirmentioning

confidence: 85%

“…Treatment of NK cells with IL-2 and anti-CD16mAb also induced split anergy by significantly decreasing the NK cell cytotoxicity while increasing the cytokine secretion capabilities of NK cells. Furthermore, NK cells exhibited CD16 -CD56 dim/-CD69 + phenotype after treatment with the combination of IL-2 and anti-CD16mAb (Jewett et al 1997(Jewett et al , 2006(Jewett et al , 2008Jewett and Bonavida 2000). Loss of cytotoxicity in NK cells was significantly exacerbated when NK cells were either treated with F(ab) 0 2 fragment of anti-CD16 mAb with IL-2 or treated with a combination of MHC-Class I and anti-CD16 mAbs in combination with IL-2 while the same treatments resulted in an increased secretion of cytokines (Jewett and Bonavida 2000;2008).…”

Section: Split Anergy In Il-2 Treated Nk Cells Is Induced After Theirmentioning

confidence: 99%

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Tumor Microenvironment may Shape the Function and Phenotype of NK Cells Through the Induction of Split Anergy and Generation of Regulatory NK Cells

Jewett

2013

The Tumor Immunoenvironment

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Cytotoxic function of NK cells is suppressed in the tumor microenvironment by a number of distinct effectors. Furthermore, decreased peripheral blood NK cell cytotoxicity has been documented in cancer patients. We have previously demonstrated evidence for the role of NK cells in specific elimination of stem cells and not their differentiated counterparts. In this regard, NK cells were found to mediate significant cytotoxicity against primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells (hESCs), human mesenchymal stem cells (hMSCs), human dental pulp stem cells (hDPSCs) and induced human pluripotent stem cells (hiPSCs) were all significantly more susceptible to NK cell mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. There is also a stage wise susceptibility to NK cell mediated cytotoxicity in pancreatic tumors in which case the poorly differentiated tumors are lysed much more than their moderately differentiated tumors. The well differentiated pancreatic tumors were lysed the least when compared to either the moderately differentiated tumors or to poorly differentiated tumors. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated stage by blocking NF-jB or gene deletion of COX2 significantly augmented NK cell cytotoxicity against both transformed and healthy cells. Therefore, we propose that the two stages of NK cell maturation namely CD16 ? CD56 dim CD69-NK cells are important for the selection of stem

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Section: Split Anergy In Il-2 Treated Nk Cells Is Induced After Theirmentioning

confidence: 85%

Section: Split Anergy In Il-2 Treated Nk Cells Is Induced After Theirmentioning

confidence: 99%

Tumor Microenvironment may Shape the Function and Phenotype of NK Cells Through the Induction of Split Anergy and Generation of Regulatory NK Cells

Jewett

2013

The Tumor Immunoenvironment

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“…Previous studies by other groups have also shown that a subset of IL-2 activated NK cells undergo cell death following crosslinking of the CD16 receptor (Azzoni et al, 1995;Ortaldo et al, 1995). Addition of antibodies to CD56 or LFA-1 did not cause any decrease in NK cell cytotoxicity, demonstrating the specificity of anti-CD16 monoclonal antibody (mAb) signaling in mediating inhibition of NK cell cytotoxicity (Jewett & Bonavida, 2000). Thus, we coined the term 'split anergy' for responses mediated by NK cells after their interaction with sensitive target cells or after the triggering of CD16 receptors by the antibody in combination with IL-2 treatment (Jewett & Bonavida, 1995Jewett et al, 1997;Jewett et al, 2006aJewett et al, , 2008 (Bonavida et al, 1993;Jewett & Bonavida, 1994.…”

Section: Cd56mentioning

confidence: 94%

“…Furthermore, NK cells exhibited a CD16 À CD56 dim/À CD69 + phenotype after treatment with the combination of IL-2 and anti-CD16 mAb (Jewett & Bonavida, 2000;Jewett et al, 1997Jewett et al, , 2006aJewett et al, , 2008. Loss of cytotoxicity in NK cells was significantly exacerbated when NK cells were either treated with F(ab)' 2 fragment of anti-CD16 mAb with IL-2 or treated with a combination of MHC Class I and anti-CD16 mAb in combination with IL-2, while the same treatments resulted in an increased secretion of cytokines (Jewett & Bonavida, 2000;Jewett et al, 2008). Based on our recent results, NKp46 mAb were also able to induce significant NK cell anergy in the presence and absence of IL-2 correlating with their increased expression on untreated and IL-2 treated NK cells (manuscript submitted).…”

Section: Cd56mentioning

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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“…β 2 m is a component of MHC class I molecule which is necessary for transport and surface expression of functional class I molecules of MHC in mice [17]. In human, coincubation of NK cells with MHC class-I-deficient target cells results in the induction of NK cell death and inhibition of NK cell cytotoxic activity [6], suggesting that MHC class I antigens regulate the function of NK cell [3,7]. Thus, the function of MHC class I antigens on target cells may be important for survival and function of the activated NK cells.…”

mentioning

confidence: 99%

Uterine Natural Killer Cells in Perforin and .BETA.2-Microglobulin Deficient Mice

Phichitrasilp

Hondo

Kusakabe

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. Uterine natural killer (uNK) cells have roles for immune responses at the feto-maternal interface in mice. We studied the effects of β 2 -microglobulin (β 2 m) and perforin on proliferation and differentiation of uNK cells in pregnancy, using β 2 -microglobulindeficient (β 2 m -/-) mice and perforin-deficient (P -/-) mice. The cell population of uNK cells in the metrial gland of P -/-mice was tended to be higher than the control B6 mice. The cell population of uNK cells in the metrial gland of β 2 m -/-mice was significantly increased at Day 12 of pregnancy comparing to B6 and P -/-mice. On the other hand, the cell population of uNK cells in the decidua basalis of β 2 m -/-mice was tended to be lower than B6 and P -/-mice. These results indicate that β 2 m may be involved in proliferation of uNK cells in the metrial gland, and that β 2 m may affect the maturation of uNK cells in the decidua basalis. KEY WORDS: β 2 -microglobulin, perforin, uterine natural killer cell.

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MHC-Class I Antigens Regulate Both the Function and the Survival of Human Peripheral Blood NK Cells: Role of Endogenously Secreted TNF-α

Cited by 23 publications

References 28 publications

Tumor Microenvironment may Shape the Function and Phenotype of NK Cells Through the Induction of Split Anergy and Generation of Regulatory NK Cells

Tumor Microenvironment may Shape the Function and Phenotype of NK Cells Through the Induction of Split Anergy and Generation of Regulatory NK Cells

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

Uterine Natural Killer Cells in Perforin and .BETA.2-Microglobulin Deficient Mice

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