Alloimmune activation enhances innate tissue inflammation/injury in a mouse model of liver ischemia/reperfusion injury

X. Shen, F. Reng, F. Gao, Y. Uchida, R. W. Busuttil, J. W. Kupiec-Weglinski, Y. Zhai

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The deleterious sensitization to donor MHC Ags represents one of the most challenging problems in clinical organ transplantation. Although the role of effector/memory T cells in the rejection cascade has been extensively studied, it remains unknown whether and how these 'Ag-specific' cells influence host innate immunity, such as tissue inflammation associated with ischemia and reperfusion injury (IRI). In this study, we analyzed how allogeneic skin transplant (Tx) affected the sequel of host's own liver damage induced by partial warm ischemia and reperfusion. Our data clearly showed that allo-Tx recipients had increased inflammatory response against IR insult in their native livers, as evidenced by significantly more severe hepatocelluar damage, compared with syngeneic Tx recipient controls, and determined by serum ALT levels, liver histology (Suzuki's score) and intrahepatic proinflammatory gene inductions (TNF-α, IL-1β and CXCL10). The CD4 T cells, but neither CD8 nor NK cells, mediated the detrimental effect of allo-Ag sensitization in liver IRI. Furthermore, CD154, but not IFN-γ, was the key mechanism in allo-Tx recipients to facilitate IR-triggered liver damage. These results provide new evidence that alloreactive CD4 T cells are capable of enhancing innate tissue inflammation and organ injury via an Ag-nonspecific CD154-dependent but IFN-γ independent mechanism.

Original languageEnglish
Pages (from-to)1729-1737
Number of pages9
JournalAmerican Journal of Transplantation
Volume10
Issue number8
DOIs
Publication statusPublished - 08-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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