Changes in the transcriptome in allograft rejection: IFN-gamma-induced transcripts in mouse kidney allografts

Am J Transplant. 2006 Jun;6(6):1342-54. doi: 10.1111/j.1600-6143.2006.01337.x.


We used Affymetrix Microarrays to define interferon-gamma (IFN-gamma)-dependent, rejection-induced transcripts (GRITs) in mouse kidney allografts. The algorithm included inducibility by recombinant IFN-gamma in kidneys of three normal mouse strains, increase in kidney allografts in three strain combinations and less induction in IFN-gamma-deficient allografts. We identified 40 transcripts, which were highly IFN-gamma inducible (e.g. Cxcl9, ubiquitin D, MHC), and 168 less sensitive to IFN-gamma in normal kidney. In allografts, expression of GRITs was intense and consistent at all time points (day 3 through 42). These transcripts were partially dependent on donor IFN-gamma receptors (IFN-gammars): receptor-deficient allografts manifested up to 76% less expression, but some transcripts were highly dependent (ubiquitin D) and others relatively independent (Cxcl9). Kidneys of hosts rejecting allografts showed expression similar to that observed with IFN-gamma injections. Many GRITs showed transient IFN-gamma-dependent increase in isografts, peaking at day 4-5. GRITs were increased in heart allografts, indicating them as generalized feature of alloresponse. Thus, expression of rejection-induced transcripts is robust and consistent in allografts, reflecting the IFN-gamma produced by the alloresponse locally and systemically, acting via host and donor IFN-gammar, as well as local IFN-gamma production induced by post-operative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Graft Rejection / immunology*
  • H-2 Antigens / immunology
  • Heart Transplantation / immunology
  • Interferon-gamma / deficiency
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology*
  • Kidney Transplantation / immunology*
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Models, Animal
  • Transcription, Genetic* / drug effects
  • Transcription, Genetic* / immunology
  • Transplantation, Homologous


  • H-2 Antigens
  • H-2Kb protein, mouse
  • Interferon-gamma