IFN-γ alters the pathology of graft rejection: Protection from early necrosis

P. F. Halloran, L. W. Miller, J. Urmson, V. Ramassar, L. F. Zhu, N. M. Kneteman, K. Solez, Marjan Afrouzian

Research output: Contribution to journalArticle

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Abstract

We studied the effect of host IFN-γ on the pathology of acute rejection of vascularized mouse heart and kidney allografts. Organs from CBA donors (H-2k) were transplanted into BALB/c (H-2d) hosts with wild-type (WT) or disrupted (GKO, BALB/c mice with disrupted IFN-γ genes) IFN-γ genes. In WT hosts, rejecting hearts and kidneys showed mononuclear cell infiltration, intense induction of donor MHC products, but little parenchymal necrosis at day 7. Rejecting allografts in GKO recipients showed infiltrate but little or no induction of donor MHC and developed extensive necrosis despite patent large vessels. The necrosis was immunologically mediated, since it developed during rejection, was absent in isografts, and was prevented by immunosuppressing the recipient with cyclosporine or mycophenolate mofetil. Rejecting kidneys in GKO hosts showed increased mRNA for heme oxygenase 1, and decreased mRNA for NO synthase 2 and monokine inducible by IFN-γ (MIG). The mRNA levels for CTL genes (perforin, granzyme B, and Fas ligand) were similar in rejecting kidneys in WT and GKO hosts, and the host Ab responses were similar. The administration of recombinant IFN-γ to GKO hosts reduced but did not fully prevent the effects of IFN-γ deficiency: MHC was induced, but the prevention of necrosis and induction of MIG were incomplete compared with WT hosts. Thus, IFN-γ has unique effects in vascularized allografts, including induction of MHC and MIG, and protection against parenchymal necrosis, probably at the level of the microcirculation. This is probably a local action of IFN-γ produced in large quantities in the allograft.

Original languageEnglish (US)
Pages (from-to)7072-7081
Number of pages10
JournalJournal of Immunology
Volume166
Issue number12
StatePublished - Jun 15 2001
Externally publishedYes

Fingerprint

Graft Rejection
Necrosis
Allografts
Pathology
Kidney
Tissue Donors
Messenger RNA
Isografts
Monokines
Genes
Mycophenolic Acid
Heme Oxygenase-1
Fas Ligand Protein
Microcirculation
Nitric Oxide Synthase
Cyclosporine

ASJC Scopus subject areas

  • Immunology

Cite this

Halloran, P. F., Miller, L. W., Urmson, J., Ramassar, V., Zhu, L. F., Kneteman, N. M., ... Afrouzian, M. (2001). IFN-γ alters the pathology of graft rejection: Protection from early necrosis. Journal of Immunology, 166(12), 7072-7081.

IFN-γ alters the pathology of graft rejection : Protection from early necrosis. / Halloran, P. F.; Miller, L. W.; Urmson, J.; Ramassar, V.; Zhu, L. F.; Kneteman, N. M.; Solez, K.; Afrouzian, Marjan.

In: Journal of Immunology, Vol. 166, No. 12, 15.06.2001, p. 7072-7081.

Research output: Contribution to journalArticle

Halloran, PF, Miller, LW, Urmson, J, Ramassar, V, Zhu, LF, Kneteman, NM, Solez, K & Afrouzian, M 2001, 'IFN-γ alters the pathology of graft rejection: Protection from early necrosis', Journal of Immunology, vol. 166, no. 12, pp. 7072-7081.
Halloran PF, Miller LW, Urmson J, Ramassar V, Zhu LF, Kneteman NM et al. IFN-γ alters the pathology of graft rejection: Protection from early necrosis. Journal of Immunology. 2001 Jun 15;166(12):7072-7081.
Halloran, P. F. ; Miller, L. W. ; Urmson, J. ; Ramassar, V. ; Zhu, L. F. ; Kneteman, N. M. ; Solez, K. ; Afrouzian, Marjan. / IFN-γ alters the pathology of graft rejection : Protection from early necrosis. In: Journal of Immunology. 2001 ; Vol. 166, No. 12. pp. 7072-7081.
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AU - Miller, L. W.

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AU - Ramassar, V.

AU - Zhu, L. F.

AU - Kneteman, N. M.

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AU - Afrouzian, Marjan

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