Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12

J Clin Invest. 1998 Dec 15;102(12):2126-35. doi: 10.1172/JCI4992.


We have demonstrated that a single injection of interleukin (IL)-12 on the day of bone marrow transplantation (BMT) inhibits acute graft-versus-host disease (GVHD) in mice. This effect of IL-12 can be diminished by anti-interferon (IFN)-gamma mAb. To determine the mechanism by which IFN-gamma affects IL-12-mediated GVHD protection, we have compared the effect of IL-12 on GVHD in C57BL/6 wild-type (WT) or IFN-gamma gene knockout (GKO) recipients of fully major histocompatibility complex plus minor antigen-mismatched allogeneic BMT from WT or GKO BALB/c mice. Lethal acute GVHD was readily induced in the absence of IFN-gamma. IL-12 inhibited GVHD mortality to a similar extent in WT and GKO recipients of WT allogeneic BMT. However, neither WT nor GKO recipients were protected by IL-12 from GVHD induced by GKO allogeneic BMT. Moreover, the effective inhibition of host-reactive donor T cell activation and expansion that is associated with IL-12-mediated GVHD protection was dependent on the ability of BALB/c donors to produce IFN-gamma. These results demonstrate that (a) acute GVHD can be induced in the absence of IFN-gamma, (b) host IFN-gamma does not play a critical role in IL-12-induced GVHD protection, and (c) the protective effect of IL-12 against GVHD is dependent on the ability of the donor to produce IFN-gamma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antigens, CD / immunology
  • Bone Marrow Transplantation / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Count / drug effects
  • Disease Models, Animal
  • Female
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / mortality
  • Interferon-gamma / immunology
  • Interleukin-12 / pharmacology*
  • Interleukin-12 / therapeutic use
  • Mice
  • Mice, Inbred Strains
  • Spleen / immunology
  • Time Factors
  • Whole-Body Irradiation


  • Antibodies
  • Antigens, CD
  • Interleukin-12
  • Interferon-gamma