Donor T cell activation initiates small bowel allograft rejection through an IFN-γ-inducible protein-10-dependent mechanism

Zheng Zhang, Levent Kaptanoglu, Wael Haddad, David Ivancic, Ziad Alnadjim, Stephen Hurst, Darren Tishler, Andrew D. Luster, Terrence A. Barrett, Jonathan Fryer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

The poor success in controlling small bowel (SB) allograft rejection is partially attributed to the unique immune environment in the donor intestine. We hypothesized that Ag-induced activation of donor-derived T cells contributes to the initiation of SB allograft rejection. To address the role of donor T cell activation in SB transplantation, SB grafts from DO11.10 TCR transgenic mice (BALB/c, H-2Ld+) were transplanted into BALB/c (isografts), or single class I MHC-mismatched (Ld-deficient) BALB/c H-2dm2 (dm2, H-2Ld-) mutant mice (allografts). Graft survival was followed after injection of control or antigenic OVA323-339 peptide. Eighty percent of SB allografts developed severe rejection in mice treated with antigenic peptide, whereas <20% of allografts were rejected in mice treated with control peptide (p < 0.05). Isografts survived >30 days regardless of OVA323-339 administration. Activation of donor T cells increased intragraft expression of proinflammatory cytokine (IFN-γ) and CXC chemokine IFN-γ-inducible protein-10 mRNA and enhanced activation and accumulation of host NK and T cells in SB allografts. Treatment of mice with neutralizing anti-IFN-γ-inducible protein-10 mAb increased SB allograft survival in Ag-treated mice (67%; p < 0.05) and reduced accumulation of host T cells and NK cells in the lamina propria but not mesenteric lymph nodes. These results suggest that activation of donor T cells after SB allotransplantation induces production of a Th1-like profile of cytokines and CXC chemokines that enhance infiltration of host T cells and NK cells in SB allografts. Blocking this pathway may be of therapeutic value in controlling SB allograft rejection.

Original languageEnglish (US)
Pages (from-to)3205-3212
Number of pages8
JournalJournal of Immunology
Volume168
Issue number7
DOIs
StatePublished - Apr 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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