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Costimulatory molecules are active in the human xenoreactive T-cell response but not in natural killer-mediated cytotoxicity.

Publication ,  Journal Article
Tadaki, DK; Craighead, N; Saini, A; Celniker, A; Burkly, LC; Lee, KP; Chute, JP; Harlan, DM; Kirk, AD
Published in: Transplantation
July 15, 2000

BACKGROUND: T-cell costimulatory blocking agents inhibit allospecific T-cell responses in vitro and prevent allograft rejection in vivo. Costimulatory requirements for discordant xenospecific cellular responses remain undefined. We have evaluated costimulatory molecule expression by porcine endothelial cells (PEC) after interaction with human cells and tested agents known to inhibit allospecific responses for their ability to inhibit xenospecific responses in vitro. METHODS: Human-specific agents were screened for their ability to bind porcine costimulatory molecules by FACS. Up-regulation of B7 molecules on PEC was evaluated by FACS after exposure to human cells or supernatants. The effect of human and/or porcine costimulatory blockade was tested in xeno-mixed lymphocyte reactions (XMLRs) and in natural killer (NK) cell cytotoxicity assays. RESULTS: B7 expression was induced on PEC after exposure to human T and NK cells or T cell-conditioned medium. The human XMLR was attenuated by human CTLA4-Ig and anti-human CD154 (hu5C8), and the combination was synergistic. Anti-human CD80 and CD86 antibodies alone had minor effects in the XMLR, but in combination with hu5C8 were as effective as human CTLA4-Ig plus hu5C8. Anti-hCD80 and hCD86 antibodies that did not cross-react with porcine CD80 or CD86 were as effective in blocking the MLR as those that did cross-react, indicating that the predominant costimulation in vitro was derived from the responding cells. None of the agents affected the xeno-NK response. CONCLUSIONS: We conclude that the costimulation-modulating agents block human anti-porcine T-cell responses in vitro predominantly through interruption of costimulation derived from responding cells. They have no effect on NK cell-mediated cytotoxicity.

Duke Scholars

Published In

Transplantation

ISSN

0041-1337

Publication Date

July 15, 2000

Volume

70

Issue

1

Start / End Page

162 / 167

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • T-Lymphocytes
  • Swine
  • Surgery
  • Membrane Glycoproteins
  • Killer Cells, Natural
  • Immunoconjugates
  • Humans
  • Endothelium, Vascular
  • Cytotoxicity, Immunologic
 

Citation

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Tadaki, D. K., Craighead, N., Saini, A., Celniker, A., Burkly, L. C., Lee, K. P., … Kirk, A. D. (2000). Costimulatory molecules are active in the human xenoreactive T-cell response but not in natural killer-mediated cytotoxicity. Transplantation, 70(1), 162–167.
Tadaki, D. K., N. Craighead, A. Saini, A. Celniker, L. C. Burkly, K. P. Lee, J. P. Chute, D. M. Harlan, and A. D. Kirk. “Costimulatory molecules are active in the human xenoreactive T-cell response but not in natural killer-mediated cytotoxicity.Transplantation 70, no. 1 (July 15, 2000): 162–67.
Tadaki DK, Craighead N, Saini A, Celniker A, Burkly LC, Lee KP, et al. Costimulatory molecules are active in the human xenoreactive T-cell response but not in natural killer-mediated cytotoxicity. Transplantation. 2000 Jul 15;70(1):162–7.
Tadaki, D. K., et al. “Costimulatory molecules are active in the human xenoreactive T-cell response but not in natural killer-mediated cytotoxicity.Transplantation, vol. 70, no. 1, July 2000, pp. 162–67.
Tadaki DK, Craighead N, Saini A, Celniker A, Burkly LC, Lee KP, Chute JP, Harlan DM, Kirk AD. Costimulatory molecules are active in the human xenoreactive T-cell response but not in natural killer-mediated cytotoxicity. Transplantation. 2000 Jul 15;70(1):162–167.

Published In

Transplantation

ISSN

0041-1337

Publication Date

July 15, 2000

Volume

70

Issue

1

Start / End Page

162 / 167

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • T-Lymphocytes
  • Swine
  • Surgery
  • Membrane Glycoproteins
  • Killer Cells, Natural
  • Immunoconjugates
  • Humans
  • Endothelium, Vascular
  • Cytotoxicity, Immunologic