Induction of swine major histocompatibility complex class I molecules on porcine endothelium by tumor necrosis factor-α reduces lysis by human natural killer cells

Pawel Kwiatkowski, John H. Artrip, Ranjit John, Niloo M. Edwards, Shu Feng Wang, Robert E. Michler, Silviu Itescu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background. Natural killer (NK) cells have been implicated in a process of delayed xenograft rejection occurring in pig-to-primate organ transplants. As tumor necrosis factor-α (TNF-α) induces expression of both adhesion receptors and major histocompatibility complex class I molecules on porcine endothelium, we investigated the effects of TNF-α on human NK cell adherence to and cytotoxicity of porcine aortic endothelial cell (PAEC) monolayers. Methods. Adherence of human NK cells was measured after PAEC treatment with increasing concentrations of TNF-α. Monoclonal antibodies (mAbs) against adhesion molecules on NK cells and PAEC were used in inhibition studies. Resting or TNF-α-treated PAEC were used as targets for NK lysis. Increasing titers of anti-swine leukocyte antigen (SLA) class I antibodies or pooled human immune globulin (IVIg) were used to reverse the effects of TNF-α on NK lysis. Results. NK cell adhesion to TNF-α-treated PAEC increased in a dose- dependent manner by a maximum of 44%, and was inhibited by mAbs against CD49d, CD11a, CD11b, CD18, and CD2, as well as porcine vascular cell adhesion molecules. In contrast, TNF-α treatment of PAEC reduced human NK lysis in a dose-dependent manner. Preincubation of TNF-α-treated PAEC with increasing concentrations of anti-SLA class I mAb increased NK lysis in a titer- dependent manner, and reversed the protective effect on human NK lysis by 77%. Treatment with Mg, containing antibodies against an α-helical region of HLA class I molecules, had a similar effect. Conclusions. These results imply that SLA class I molecules can bind to inhibitory receptors on human NK cells, and that these interactions can be augmented by increasing the level of SLA class I molecule expression on porcine endothelium. Strategies that can increase porcine endothelial cell expression of either swine or human major histocompatibility complex class I molecules may reduce human NK activity against porcine xenografts.

Original languageEnglish (US)
Pages (from-to)211-218
Number of pages8
JournalTransplantation
Volume67
Issue number2
DOIs
StatePublished - Jan 27 1999
Externally publishedYes

Fingerprint

Major Histocompatibility Complex
Natural Killer Cells
Endothelium
Swine
Tumor Necrosis Factor-alpha
Endothelial Cells
Heterografts
Monoclonal Antibodies
Vascular Cell Adhesion Molecule-1
Immunoglobulin Isotypes
Cell Adhesion
Cell Communication
Primates
Immunoglobulins

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Induction of swine major histocompatibility complex class I molecules on porcine endothelium by tumor necrosis factor-α reduces lysis by human natural killer cells. / Kwiatkowski, Pawel; Artrip, John H.; John, Ranjit; Edwards, Niloo M.; Wang, Shu Feng; Michler, Robert E.; Itescu, Silviu.

In: Transplantation, Vol. 67, No. 2, 27.01.1999, p. 211-218.

Research output: Contribution to journalArticle

Kwiatkowski, Pawel ; Artrip, John H. ; John, Ranjit ; Edwards, Niloo M. ; Wang, Shu Feng ; Michler, Robert E. ; Itescu, Silviu. / Induction of swine major histocompatibility complex class I molecules on porcine endothelium by tumor necrosis factor-α reduces lysis by human natural killer cells. In: Transplantation. 1999 ; Vol. 67, No. 2. pp. 211-218.
@article{f657ca1d564c43ce9252d71cae4c6344,
title = "Induction of swine major histocompatibility complex class I molecules on porcine endothelium by tumor necrosis factor-α reduces lysis by human natural killer cells",
abstract = "Background. Natural killer (NK) cells have been implicated in a process of delayed xenograft rejection occurring in pig-to-primate organ transplants. As tumor necrosis factor-α (TNF-α) induces expression of both adhesion receptors and major histocompatibility complex class I molecules on porcine endothelium, we investigated the effects of TNF-α on human NK cell adherence to and cytotoxicity of porcine aortic endothelial cell (PAEC) monolayers. Methods. Adherence of human NK cells was measured after PAEC treatment with increasing concentrations of TNF-α. Monoclonal antibodies (mAbs) against adhesion molecules on NK cells and PAEC were used in inhibition studies. Resting or TNF-α-treated PAEC were used as targets for NK lysis. Increasing titers of anti-swine leukocyte antigen (SLA) class I antibodies or pooled human immune globulin (IVIg) were used to reverse the effects of TNF-α on NK lysis. Results. NK cell adhesion to TNF-α-treated PAEC increased in a dose- dependent manner by a maximum of 44{\%}, and was inhibited by mAbs against CD49d, CD11a, CD11b, CD18, and CD2, as well as porcine vascular cell adhesion molecules. In contrast, TNF-α treatment of PAEC reduced human NK lysis in a dose-dependent manner. Preincubation of TNF-α-treated PAEC with increasing concentrations of anti-SLA class I mAb increased NK lysis in a titer- dependent manner, and reversed the protective effect on human NK lysis by 77{\%}. Treatment with Mg, containing antibodies against an α-helical region of HLA class I molecules, had a similar effect. Conclusions. These results imply that SLA class I molecules can bind to inhibitory receptors on human NK cells, and that these interactions can be augmented by increasing the level of SLA class I molecule expression on porcine endothelium. Strategies that can increase porcine endothelial cell expression of either swine or human major histocompatibility complex class I molecules may reduce human NK activity against porcine xenografts.",
author = "Pawel Kwiatkowski and Artrip, {John H.} and Ranjit John and Edwards, {Niloo M.} and Wang, {Shu Feng} and Michler, {Robert E.} and Silviu Itescu",
year = "1999",
month = "1",
day = "27",
doi = "10.1097/00007890-199901270-00005",
language = "English (US)",
volume = "67",
pages = "211--218",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Induction of swine major histocompatibility complex class I molecules on porcine endothelium by tumor necrosis factor-α reduces lysis by human natural killer cells

AU - Kwiatkowski, Pawel

AU - Artrip, John H.

AU - John, Ranjit

AU - Edwards, Niloo M.

AU - Wang, Shu Feng

AU - Michler, Robert E.

AU - Itescu, Silviu

PY - 1999/1/27

Y1 - 1999/1/27

N2 - Background. Natural killer (NK) cells have been implicated in a process of delayed xenograft rejection occurring in pig-to-primate organ transplants. As tumor necrosis factor-α (TNF-α) induces expression of both adhesion receptors and major histocompatibility complex class I molecules on porcine endothelium, we investigated the effects of TNF-α on human NK cell adherence to and cytotoxicity of porcine aortic endothelial cell (PAEC) monolayers. Methods. Adherence of human NK cells was measured after PAEC treatment with increasing concentrations of TNF-α. Monoclonal antibodies (mAbs) against adhesion molecules on NK cells and PAEC were used in inhibition studies. Resting or TNF-α-treated PAEC were used as targets for NK lysis. Increasing titers of anti-swine leukocyte antigen (SLA) class I antibodies or pooled human immune globulin (IVIg) were used to reverse the effects of TNF-α on NK lysis. Results. NK cell adhesion to TNF-α-treated PAEC increased in a dose- dependent manner by a maximum of 44%, and was inhibited by mAbs against CD49d, CD11a, CD11b, CD18, and CD2, as well as porcine vascular cell adhesion molecules. In contrast, TNF-α treatment of PAEC reduced human NK lysis in a dose-dependent manner. Preincubation of TNF-α-treated PAEC with increasing concentrations of anti-SLA class I mAb increased NK lysis in a titer- dependent manner, and reversed the protective effect on human NK lysis by 77%. Treatment with Mg, containing antibodies against an α-helical region of HLA class I molecules, had a similar effect. Conclusions. These results imply that SLA class I molecules can bind to inhibitory receptors on human NK cells, and that these interactions can be augmented by increasing the level of SLA class I molecule expression on porcine endothelium. Strategies that can increase porcine endothelial cell expression of either swine or human major histocompatibility complex class I molecules may reduce human NK activity against porcine xenografts.

AB - Background. Natural killer (NK) cells have been implicated in a process of delayed xenograft rejection occurring in pig-to-primate organ transplants. As tumor necrosis factor-α (TNF-α) induces expression of both adhesion receptors and major histocompatibility complex class I molecules on porcine endothelium, we investigated the effects of TNF-α on human NK cell adherence to and cytotoxicity of porcine aortic endothelial cell (PAEC) monolayers. Methods. Adherence of human NK cells was measured after PAEC treatment with increasing concentrations of TNF-α. Monoclonal antibodies (mAbs) against adhesion molecules on NK cells and PAEC were used in inhibition studies. Resting or TNF-α-treated PAEC were used as targets for NK lysis. Increasing titers of anti-swine leukocyte antigen (SLA) class I antibodies or pooled human immune globulin (IVIg) were used to reverse the effects of TNF-α on NK lysis. Results. NK cell adhesion to TNF-α-treated PAEC increased in a dose- dependent manner by a maximum of 44%, and was inhibited by mAbs against CD49d, CD11a, CD11b, CD18, and CD2, as well as porcine vascular cell adhesion molecules. In contrast, TNF-α treatment of PAEC reduced human NK lysis in a dose-dependent manner. Preincubation of TNF-α-treated PAEC with increasing concentrations of anti-SLA class I mAb increased NK lysis in a titer- dependent manner, and reversed the protective effect on human NK lysis by 77%. Treatment with Mg, containing antibodies against an α-helical region of HLA class I molecules, had a similar effect. Conclusions. These results imply that SLA class I molecules can bind to inhibitory receptors on human NK cells, and that these interactions can be augmented by increasing the level of SLA class I molecule expression on porcine endothelium. Strategies that can increase porcine endothelial cell expression of either swine or human major histocompatibility complex class I molecules may reduce human NK activity against porcine xenografts.

UR - http://www.scopus.com/inward/record.url?scp=0033608091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033608091&partnerID=8YFLogxK

U2 - 10.1097/00007890-199901270-00005

DO - 10.1097/00007890-199901270-00005

M3 - Article

VL - 67

SP - 211

EP - 218

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 2

ER -