Interleukin-2 and interferon-gamma double knockout mice reject heterotopic cardiac allografts.
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.
Zand
M S
MS
Division of Immunology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. martin_zand@urmc.rochester.edu
Li
Y
Y
Hancock
W
W
Li
X C
XC
Roy-Chaudhury
P
P
Zheng
X X
XX
Strom
T B
TB
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
D007376:Interleukin-2; D007371:Interferon-gamma