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Transplantation. 1999 May 27;67(10):1362-5.

Interferon-gamma is necessary for initiating the acute rejection of major histocompatibility complex class II-disparate skin allografts.

Author information

1
The Carlos and Marguerite Mason Transplantation Research Center, The Atlanta Veterans Affairs Medical Center, Department of Medicine, Emory University, Georgia 30033, USA.

Abstract

BACKGROUND:

Although interferon (IFN)gamma has immunostimulatory functions, it is not essential for the acute rejection of fully allogeneic grafts in mice. It is not known whether IFNgamma plays a critical role in the acute rejection of MHC class I- or MHC class II-disparate allografts.

METHODS:

We studied the survival of skin allografts transplanted from fully allogeneic (BALB/c), MHC class I-disparate (bml), or MHC class II-disparate (bm12) donors to C57BL/6 wild-type (IFNgamma+/+) and IFNgamma gene-knockout (IFNgamma-/-) recipients. We also investigated the in vitro responses of IFNgamma+/+ and IFNgamma-/- T cells to MHC class II-disparate splenocytes.

RESULTS:

We found that IFNgamma-/- recipients reject BALB/c and bml skin grafts at the same rate as IFNgamma+/+ mice but are not capable of rejecting bm12 skin. Despite the inability of IFNgamma-/- mice to reject bm12 skin grafts, IFNgamma-/- T cells displayed vigorous proliferation and cytotoxic responses when stimulated with bm12 splenocytes in vitro. Furthermore, priming IFNgamma-/- recipients with bm12 splenocytes enabled these mice to reject bm12 skin grafts at a normal rate and to mount a cutaneous delayed-type hypersensitivity response to the bm12 antigen.

CONCLUSION:

The data demonstrate that IFNgamma is not necessary for generating effector mechanisms associated with acute transplant rejection but that it is required for initiating alloimmune responses to MHC class II-disparate skin grafts.

[Indexed for MEDLINE]

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