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Transplantation. 2000 Nov 15;70(9):1378-81.

Interleukin-2 and interferon-gamma double knockout mice reject heterotopic cardiac allografts.

Author information

  • 1Division of Immunology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. martin_zand@urmc.rochester.edu

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.

CONCLUSION:

The combined absence of IL-2 and IFN-gamma in the setting of Th2 deviation does not prevent allograft rejection.

PMID:
11087156
[PubMed - indexed for MEDLINE]
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