Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts

Denis A. Tereb, Nancy C. Kirkiles-Smith, Richard W. Kim, Yinong Wang, Radu Daniel Rudic, Jeffrey S. Schechner, Marc I. Lorber, Alfred L.M. Bothwell, Jordan S. Pober, George Tellides

Research output: Contribution to journalArticle

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Abstract

Background. We have previously demonstrated that human artery grafts transplanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porcine xenoresponses in this model. Methods. Pig coronary artery segments were interposed into the infrarenal aorta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes and/or treated with proinflammatory cytokines. The grafts were harvested after 1-70 days and examined by histology, immunohistochemistry, and morphometry. Results. Pig artery grafts from untreated mice had no evidence of injury, leukocytic infiltrate, or endothelial cell activation up to 70 days postoperatively, despite deposition of murine complement. Host reconstitution with human peripheral blood mononuclear cells resulted in a discrete population of circulating T cells that did not infiltrate or injure the grafts up to 28 days after adoptive transfer. Administration of porcine interferon-γ for up to 28 days sustained the expression of graft vascular cell adhesion molecule-1 and major histocompatibility complex antigens, but did not initiate recruitment of human leukocytes. In contrast, treatment with human tumor necrosis factor for 7 days induced the de novo expression of porcine E-selectin by graft endothelial cells and elicited human T cell infiltration and human peripheral blood mononuclear cell-dependent vascular injury. Conclusions. The human peripheral blood mononuclear cell-severe combined immunodeficiency/beige mouse model identifies a significant difference between human T cell allogeneic and xenogeneic responses in vivo. Xenografts with quiescent endothelium are not infiltrated or injured by T cells under the same conditions in which allografts are rejected. Activation of pig coronary artery endothelial cells by human tumor necrosis factor, but not porcine interferon-γ, elicits cellular xenoresponses.

Original languageEnglish (US)
Pages (from-to)1622-1630
Number of pages9
JournalTransplantation
Volume71
Issue number11
DOIs
StatePublished - Jun 15 2001
Externally publishedYes

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Endothelium
Coronary Vessels
Swine
T-Lymphocytes
Transplants
Severe Combined Immunodeficiency
Blood Cells
Endothelial Cells
Interferons
Leukocytes
Arteries
Histocompatibility Antigens
E-Selectin
Adoptive Transfer
Vascular Cell Adhesion Molecule-1
Vascular System Injuries
Major Histocompatibility Complex
Heterografts
Allografts
Aorta

ASJC Scopus subject areas

  • Transplantation

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Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts. / Tereb, Denis A.; Kirkiles-Smith, Nancy C.; Kim, Richard W.; Wang, Yinong; Rudic, Radu Daniel; Schechner, Jeffrey S.; Lorber, Marc I.; Bothwell, Alfred L.M.; Pober, Jordan S.; Tellides, George.

In: Transplantation, Vol. 71, No. 11, 15.06.2001, p. 1622-1630.

Research output: Contribution to journalArticle

Tereb, DA, Kirkiles-Smith, NC, Kim, RW, Wang, Y, Rudic, RD, Schechner, JS, Lorber, MI, Bothwell, ALM, Pober, JS & Tellides, G 2001, 'Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts', Transplantation, vol. 71, no. 11, pp. 1622-1630. https://doi.org/10.1097/00007890-200106150-00023
Tereb, Denis A. ; Kirkiles-Smith, Nancy C. ; Kim, Richard W. ; Wang, Yinong ; Rudic, Radu Daniel ; Schechner, Jeffrey S. ; Lorber, Marc I. ; Bothwell, Alfred L.M. ; Pober, Jordan S. ; Tellides, George. / Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts. In: Transplantation. 2001 ; Vol. 71, No. 11. pp. 1622-1630.
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abstract = "Background. We have previously demonstrated that human artery grafts transplanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porcine xenoresponses in this model. Methods. Pig coronary artery segments were interposed into the infrarenal aorta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes and/or treated with proinflammatory cytokines. The grafts were harvested after 1-70 days and examined by histology, immunohistochemistry, and morphometry. Results. Pig artery grafts from untreated mice had no evidence of injury, leukocytic infiltrate, or endothelial cell activation up to 70 days postoperatively, despite deposition of murine complement. Host reconstitution with human peripheral blood mononuclear cells resulted in a discrete population of circulating T cells that did not infiltrate or injure the grafts up to 28 days after adoptive transfer. Administration of porcine interferon-γ for up to 28 days sustained the expression of graft vascular cell adhesion molecule-1 and major histocompatibility complex antigens, but did not initiate recruitment of human leukocytes. In contrast, treatment with human tumor necrosis factor for 7 days induced the de novo expression of porcine E-selectin by graft endothelial cells and elicited human T cell infiltration and human peripheral blood mononuclear cell-dependent vascular injury. Conclusions. The human peripheral blood mononuclear cell-severe combined immunodeficiency/beige mouse model identifies a significant difference between human T cell allogeneic and xenogeneic responses in vivo. Xenografts with quiescent endothelium are not infiltrated or injured by T cells under the same conditions in which allografts are rejected. Activation of pig coronary artery endothelial cells by human tumor necrosis factor, but not porcine interferon-γ, elicits cellular xenoresponses.",
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T1 - Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts

AU - Tereb, Denis A.

AU - Kirkiles-Smith, Nancy C.

AU - Kim, Richard W.

AU - Wang, Yinong

AU - Rudic, Radu Daniel

AU - Schechner, Jeffrey S.

AU - Lorber, Marc I.

AU - Bothwell, Alfred L.M.

AU - Pober, Jordan S.

AU - Tellides, George

PY - 2001/6/15

Y1 - 2001/6/15

N2 - Background. We have previously demonstrated that human artery grafts transplanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porcine xenoresponses in this model. Methods. Pig coronary artery segments were interposed into the infrarenal aorta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes and/or treated with proinflammatory cytokines. The grafts were harvested after 1-70 days and examined by histology, immunohistochemistry, and morphometry. Results. Pig artery grafts from untreated mice had no evidence of injury, leukocytic infiltrate, or endothelial cell activation up to 70 days postoperatively, despite deposition of murine complement. Host reconstitution with human peripheral blood mononuclear cells resulted in a discrete population of circulating T cells that did not infiltrate or injure the grafts up to 28 days after adoptive transfer. Administration of porcine interferon-γ for up to 28 days sustained the expression of graft vascular cell adhesion molecule-1 and major histocompatibility complex antigens, but did not initiate recruitment of human leukocytes. In contrast, treatment with human tumor necrosis factor for 7 days induced the de novo expression of porcine E-selectin by graft endothelial cells and elicited human T cell infiltration and human peripheral blood mononuclear cell-dependent vascular injury. Conclusions. The human peripheral blood mononuclear cell-severe combined immunodeficiency/beige mouse model identifies a significant difference between human T cell allogeneic and xenogeneic responses in vivo. Xenografts with quiescent endothelium are not infiltrated or injured by T cells under the same conditions in which allografts are rejected. Activation of pig coronary artery endothelial cells by human tumor necrosis factor, but not porcine interferon-γ, elicits cellular xenoresponses.

AB - Background. We have previously demonstrated that human artery grafts transplanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porcine xenoresponses in this model. Methods. Pig coronary artery segments were interposed into the infrarenal aorta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes and/or treated with proinflammatory cytokines. The grafts were harvested after 1-70 days and examined by histology, immunohistochemistry, and morphometry. Results. Pig artery grafts from untreated mice had no evidence of injury, leukocytic infiltrate, or endothelial cell activation up to 70 days postoperatively, despite deposition of murine complement. Host reconstitution with human peripheral blood mononuclear cells resulted in a discrete population of circulating T cells that did not infiltrate or injure the grafts up to 28 days after adoptive transfer. Administration of porcine interferon-γ for up to 28 days sustained the expression of graft vascular cell adhesion molecule-1 and major histocompatibility complex antigens, but did not initiate recruitment of human leukocytes. In contrast, treatment with human tumor necrosis factor for 7 days induced the de novo expression of porcine E-selectin by graft endothelial cells and elicited human T cell infiltration and human peripheral blood mononuclear cell-dependent vascular injury. Conclusions. The human peripheral blood mononuclear cell-severe combined immunodeficiency/beige mouse model identifies a significant difference between human T cell allogeneic and xenogeneic responses in vivo. Xenografts with quiescent endothelium are not infiltrated or injured by T cells under the same conditions in which allografts are rejected. Activation of pig coronary artery endothelial cells by human tumor necrosis factor, but not porcine interferon-γ, elicits cellular xenoresponses.

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