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Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses.

Publication ,  Journal Article
Li, S; Anwar, IJ; Canning, AJ; Vo-Dinh, T; Kirk, AD; Xu, H
Published in: Am J Transplant
July 2023

Porcine vascular endothelial cells (PECs) form a mechanistic centerpiece of xenograft rejection. Here, we determined that resting PECs release swine leukocyte antigen class I (SLA-I) but not swine leukocyte antigen class-II DR (SLA-DR) expressing extracellular vesicles (EVs) and investigated whether these EVs proficiently initiate xenoreactive T cell responses via direct xenorecognition and costimulation. Human T cells acquired SLA-I+ EVs with or without direct contact to PECs, and these EVs colocalized with T cell receptors. Although interferon gamma-activated PECs released SLA-DR+ EVs, the binding of SLA-DR+ EVs to T cells was sparse. Human T cells demonstrated low levels of proliferation without direct contact to PECs, but marked T cell proliferation was induced following exposure to EVs. EV-induced proliferation proceeded independent of monocytes/macrophages, suggesting that EVs delivered both a T cell receptor signal and costimulation. Costimulation blockade targeting B7, CD40L, or CD11a significantly reduced T cell proliferation to PEC-derived EVs. These findings indicate that endothelial-derived EVs can directly initiate T cell-mediated immune responses, and suggest that inhibiting the release of SLA-I EVs from organ xenografts has the potential to modify the xenograft rejection. We propose a secondary-direct pathway for T cell activation via xenoantigen recognition/costimulation by endothelial-derived EVs.

Duke Scholars

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Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

July 2023

Volume

23

Issue

7

Start / End Page

904 / 919

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Swine
  • Surgery
  • Immunity
  • Humans
  • Histocompatibility Antigens Class I
  • Endothelium
  • Endothelial Cells
  • Animals
  • 3204 Immunology
 

Citation

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Li, S., Anwar, I. J., Canning, A. J., Vo-Dinh, T., Kirk, A. D., & Xu, H. (2023). Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses. Am J Transplant, 23(7), 904–919. https://doi.org/10.1016/j.ajt.2023.04.006
Li, Shu, Imran J. Anwar, Aidan J. Canning, Tuan Vo-Dinh, Allan D. Kirk, and He Xu. “Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses.Am J Transplant 23, no. 7 (July 2023): 904–19. https://doi.org/10.1016/j.ajt.2023.04.006.
Li, Shu, et al. “Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses.Am J Transplant, vol. 23, no. 7, July 2023, pp. 904–19. Pubmed, doi:10.1016/j.ajt.2023.04.006.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

July 2023

Volume

23

Issue

7

Start / End Page

904 / 919

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Swine
  • Surgery
  • Immunity
  • Humans
  • Histocompatibility Antigens Class I
  • Endothelium
  • Endothelial Cells
  • Animals
  • 3204 Immunology