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Porcine embryonic brain cell cytotoxicity mediated by human natural killer cells

Sumitran-Holgersson, S; Anderson, P; Widner, H LU and Holgersson, J. (1999) In Cell Transplantation 8(6). p.10-601
Abstract

Intracerebral transplantation of porcine embryonic dopamine-producing neurons has been suggested as a method to treat patients with Parkinson's disease. Even though the brain is an immunologically privileged site, neuronal xenografts are usually rejected within a few weeks. T cells are important for this process, but the exact cellular events leading to rejection are poorly characterized. Brain cells from ventral mesencephalon of 26-27-day-old pig embryos were used as target cells in flow cytometry-assessed cytotoxicity assays using non- and IL-2-activated CD3- CD16+ CD56+ human natural killer (NK) cells as effector cells. The ability of human NK cells to kill pig embryonic brain cells by antibody-dependent cellular cytotoxicity (ADCC)... (More)

Intracerebral transplantation of porcine embryonic dopamine-producing neurons has been suggested as a method to treat patients with Parkinson's disease. Even though the brain is an immunologically privileged site, neuronal xenografts are usually rejected within a few weeks. T cells are important for this process, but the exact cellular events leading to rejection are poorly characterized. Brain cells from ventral mesencephalon of 26-27-day-old pig embryos were used as target cells in flow cytometry-assessed cytotoxicity assays using non- and IL-2-activated CD3- CD16+ CD56+ human natural killer (NK) cells as effector cells. The ability of human NK cells to kill pig embryonic brain cells by antibody-dependent cellular cytotoxicity (ADCC) in the presence of nondepleted and anti-Gal alpha1,3Gal antibody-depleted human blood group AB serum (AB serum) was evaluated using the same assay. Both nondepleted and anti-Gal alpha1,3Gal antibody-depleted AB serum could mediate ADCC of pig embryonic VM cells when human NK cells were used as effector cells. Nonactivated NK cells did not show any direct cytotoxic effect on freshly isolated VM cells, whereas IL-2-activated NK cells killed approximately 50% of the VM cells at an effector-to-target ratio of 50:1 in a 4-h cytotoxicity assay. Activation of VM cells by TNF-alpha did not change their sensitivity to human NK cell cytotoxicity. Human NK cells may thus contribute to a cellular rejection of pig neuronal xenografts by ADCC, or following IL-2 activation, by a direct cytotoxic effect.

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organization
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published
subject
keywords
ABO Blood-Group System, Animals, Antibody-Dependent Cell Cytotoxicity, Brain, Brain Tissue Transplantation, Cytotoxicity, Immunologic, Embryo, Mammalian, Fetal Tissue Transplantation, Histocompatibility Antigens Class I, Humans, In Vitro Techniques, Interleukin-2, Killer Cells, Natural, Mesencephalon, Neurons, Parkinson Disease, Swine, Transplantation, Heterologous, Tumor Necrosis Factor-alpha, Journal Article, Research Support, Non-U.S. Gov't
in
Cell Transplantation
volume
8
issue
6
pages
10 pages
publisher
Cognizant Communication Corporation
external identifiers
  • scopus:0033389508
ISSN
0963-6897
language
English
LU publication?
yes
id
eadda09e-7f3d-44db-b2c6-b9a609f15f42
date added to LUP
2017-04-19 18:21:42
date last changed
2017-06-04 04:59:04
@article{eadda09e-7f3d-44db-b2c6-b9a609f15f42,
  abstract     = {<p>Intracerebral transplantation of porcine embryonic dopamine-producing neurons has been suggested as a method to treat patients with Parkinson's disease. Even though the brain is an immunologically privileged site, neuronal xenografts are usually rejected within a few weeks. T cells are important for this process, but the exact cellular events leading to rejection are poorly characterized. Brain cells from ventral mesencephalon of 26-27-day-old pig embryos were used as target cells in flow cytometry-assessed cytotoxicity assays using non- and IL-2-activated CD3- CD16+ CD56+ human natural killer (NK) cells as effector cells. The ability of human NK cells to kill pig embryonic brain cells by antibody-dependent cellular cytotoxicity (ADCC) in the presence of nondepleted and anti-Gal alpha1,3Gal antibody-depleted human blood group AB serum (AB serum) was evaluated using the same assay. Both nondepleted and anti-Gal alpha1,3Gal antibody-depleted AB serum could mediate ADCC of pig embryonic VM cells when human NK cells were used as effector cells. Nonactivated NK cells did not show any direct cytotoxic effect on freshly isolated VM cells, whereas IL-2-activated NK cells killed approximately 50% of the VM cells at an effector-to-target ratio of 50:1 in a 4-h cytotoxicity assay. Activation of VM cells by TNF-alpha did not change their sensitivity to human NK cell cytotoxicity. Human NK cells may thus contribute to a cellular rejection of pig neuronal xenografts by ADCC, or following IL-2 activation, by a direct cytotoxic effect.</p>},
  author       = {Sumitran-Holgersson, S and Anderson, P and Widner, H and Holgersson, J.},
  issn         = {0963-6897},
  keyword      = {ABO Blood-Group System,Animals,Antibody-Dependent Cell Cytotoxicity,Brain,Brain Tissue Transplantation,Cytotoxicity, Immunologic,Embryo, Mammalian,Fetal Tissue Transplantation,Histocompatibility Antigens Class I,Humans,In Vitro Techniques,Interleukin-2,Killer Cells, Natural,Mesencephalon,Neurons,Parkinson Disease,Swine,Transplantation, Heterologous,Tumor Necrosis Factor-alpha,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {6},
  pages        = {10--601},
  publisher    = {Cognizant Communication Corporation},
  series       = {Cell Transplantation},
  title        = {Porcine embryonic brain cell cytotoxicity mediated by human natural killer cells},
  volume       = {8},
  year         = {1999},
}