Reperfusion injury intensifies the adaptive human T cell alloresponse in a human-mouse chimeric artery model

Tai Yi, Birgit Fogal, Zhengrong Hao, Zuzana Tobiasova, Chen Wang, Deepak A. Rao, Rafia S. Al-Lamki, Nancy C. Kirkiles-Smith, Sanjay Kulkarni, John R. Bradley, Alfred L.M. Bothwell, William C. Sessa, George Tellides, Jordan S. Pober

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Objective-: Perioperative nonimmune injuries to an allograft can decrease graft survival. We have developed a model for studying this process using human materials. Methods and Results-: Human artery segments were transplanted as infrarenal aortic interposition grafts into an immunodeficient mouse host, allowed to "heal in" for 30 days, and then retransplanted into a second mouse host. To induce a reperfusion injury, the healed-in artery segments were incubated for 3 hours under hypoxic conditions ex vivo before retransplantation. To induce immunologic rejection, the animals receiving the retransplanted artery segment were adoptively transferred with human peripheral blood mononuclear cells or purified T cells from a donor allogeneic to the artery 1 week before surgery. To compare rejection of injured versus healthy tissues, these manipulations were combined. Results were analyzed ex vivo by histology, morphometry, immunohistochemistry, and mRNA quantitation or in vivo by ultrasound. Our results showed that reperfusion injury, which otherwise heals with minimal sequelae, intensifies the degree of allogeneic T cell-mediated injury to human artery segments. Conclusion-: We developed a new human-mouse chimeric model demonstrating interactions of reperfusion injury and alloimmunity using human cells and tissues that may be adapted to study other forms of nonimmune injury and other types of adaptive immune responses.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • graft arteriosclerosis
  • humanized arterial mouse model
  • hypoxia
  • reperfusion injury
  • transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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