Key result
IL-2 and IFN-gamma double knockout delays cardiac allograft rejection versus wild-type mice but not IL-2 knockouts.
Why the study?
Previous models of MHC-mismatched allograft rejection have low-level expression of Th1 cytokines IL-2 and IFN-gamma, and the role of their combined absence in rejection was unclear.
p-value: p=<0.01
The combined absence of IL-2 and IFN-gamma in the setting of Th2 deviation does not prevent cardiac allograft rejection in mice.
Rejection occurs in IL-2/IFN-γ DKO mice with Th2 deviation; leaves open alternative pathways for cardiac allograft rejection.
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.
No takes yet. Share an insight, caveat, or question.
Zand et al. (2000) studied Heterotopic cardiac allograft rejection. IL-2 + IFN-gamma double knockout (DKO) vs. WT, IL-2 KO, and IFN-gamma KO mice was evaluated on Heterotopic cardiac allograft rejection time (p=<0.01). IL-2 and IFN-gamma double knockout mice rejected heterotopic cardiac allografts faster than IL-2 knockout mice, but significantly slower than wild-type and IFN-gamma knockout mice (P<0.01).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: