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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Gene Deletion, Graft Rejection, Heart Transplantation, Interferon-gamma, Interleukin-2, Mice, Mice, Knockout, Phenotype, Transplantation, Heterotopic.
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Do interleukin-2 and interferon-gamma double knockout mice reject heterotopic cardiac allografts? Context: 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). 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. 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.
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The combined absence of IL-2 and IFN-gamma in the setting of Th2 deviation does not prevent allograft rejection. Final Decision: yes