title: Interleukin-2 and interferon-gamma double knockout mice reject heterotopic cardiac allografts.
abstract: BACKGROUND
  Several studies suggest that MHC-mismatched allografts reject with a Th1 or Th2 immune response, but these models all have low-level expression of the Th1 cytokines interleukin (IL)-2 and interferon-gamma (IFN-gamma).
  
  
  METHODS
  We interbred mice with single targeted gene disruptions for IL-2 and IFN-gamma to establish IL-2 + IFN-gamma double knockout (DKO) mice. Heterotopic cardiac allografts from DBA/2j (H2d) donors were transplanted WT, IL-2 knockout (KO), IFN-gamma KO, and DKO recipients (C57BL/6x129; H2b). Cytokine transcripts from allografts and DKO splenocytes were analyzed by reverse transcription polymerase chain reaction.
  
  
  RESULTS
  DKO mice had a cytokine profile and IgG1/ IgG2a isotype ratio characteristic of Th2 deviation. DKO recipients rejected heterotopic cardiac allografts faster than IL-2 KO mice, but significantly slower than WT and IFN-gamma KO mice (P<0.01). Analysis of the rejecting DKO recipients showed intragraft Th2 cytokine expression.
  
  
  CONCLUSIONS
  The combined absence of IL-2 and IFN-gamma in the setting of Th2 deviation does not prevent allograft rejection.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. martin_zand@urmc.rochester.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Zand
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Hancock
authors.forename: X C
authors.initials: XC
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Roy-Chaudhury
authors.forename: X X
authors.initials: XX
authors.lastname: Zheng
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
mesh_terms: D000818:Animals; D017353:Gene Deletion; D006084:Graft Rejection / Q000235:genetics; D016027:Heart Transplantation / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D010641:Phenotype; D016042:Transplantation, Heterotopic
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma