Ring G H, Saleem S, Dai Z, Hassan A T, Konieczny B T, Baddoura F K, Lakkis F G
The Carlos and Marguerite Mason Transplantation Research Center, The Atlanta Veterans Affairs Medical Center, Department of Medicine, Emory University, Georgia 30033, USA.
Transplantation. 1999 May 27;67(10):1362-5. doi: 10.1097/00007890-199905270-00012.
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.
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.
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.
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.
尽管干扰素（IFN）γ具有免疫刺激功能，但它对于小鼠完全异基因移植物的急性排斥反应并非必不可少。目前尚不清楚IFNγ在MHC I类或MHC II类不相合的同种异体移植物的急性排斥反应中是否起关键作用。
我们研究了从完全异基因（BALB/c）、MHC I类不相合（bml）或MHC II类不相合（bm12）供体移植到C57BL/6野生型（IFNγ+/+）和IFNγ基因敲除（IFNγ-/-）受体的皮肤同种异体移植物的存活情况。我们还研究了IFNγ+/+和IFNγ-/- T细胞对MHC II类不相合脾细胞的体外反应。
我们发现，IFNγ-/-受体排斥BALB/c和bml皮肤移植物的速度与IFNγ+/+小鼠相同，但不能排斥bm12皮肤。尽管IFNγ-/-小鼠无法排斥bm12皮肤移植物，但IFNγ-/- T细胞在体外受到bm12脾细胞刺激时表现出强烈的增殖和细胞毒性反应。此外，用bm12脾细胞对IFNγ-/-受体进行预处理，使这些小鼠能够以正常速度排斥bm12皮肤移植物，并对bm12抗原产生皮肤迟发型超敏反应。
数据表明，IFNγ对于产生与急性移植排斥相关的效应机制并非必需，但对于启动对MHC II类不相合皮肤移植物的同种免疫反应是必需的。
