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

56 Scopus citations


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
Issue number7
StatePublished - Apr 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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