Famulski K S, Einecke G, Reeve J, Ramassar V, Allanach K, Mueller T, Hidalgo L G, Zhu L-F, Halloran P F
Department of Medicine, Division of Nephrology & Transplantation Immunology, University of Alberta, Edmonton, Alberta, Canada.
Am J Transplant. 2006 Jun;6(6):1342-54. doi: 10.1111/j.1600-6143.2006.01337.x.
We used Affymetrix Microarrays to define interferon-gamma (IFN-gamma)-dependent, rejection-induced transcripts (GRITs) in mouse kidney allografts. The algorithm included inducibility by recombinant IFN-gamma in kidneys of three normal mouse strains, increase in kidney allografts in three strain combinations and less induction in IFN-gamma-deficient allografts. We identified 40 transcripts, which were highly IFN-gamma inducible (e.g. Cxcl9, ubiquitin D, MHC), and 168 less sensitive to IFN-gamma in normal kidney. In allografts, expression of GRITs was intense and consistent at all time points (day 3 through 42). These transcripts were partially dependent on donor IFN-gamma receptors (IFN-gammars): receptor-deficient allografts manifested up to 76% less expression, but some transcripts were highly dependent (ubiquitin D) and others relatively independent (Cxcl9). Kidneys of hosts rejecting allografts showed expression similar to that observed with IFN-gamma injections. Many GRITs showed transient IFN-gamma-dependent increase in isografts, peaking at day 4-5. GRITs were increased in heart allografts, indicating them as generalized feature of alloresponse. Thus, expression of rejection-induced transcripts is robust and consistent in allografts, reflecting the IFN-gamma produced by the alloresponse locally and systemically, acting via host and donor IFN-gammar, as well as local IFN-gamma production induced by post-operative stress.
我们使用Affymetrix微阵列来定义小鼠肾移植中干扰素-γ（IFN-γ）依赖性、排斥诱导转录本（GRITs）。该算法包括在三种正常小鼠品系的肾脏中重组IFN-γ的诱导性、三种品系组合中肾移植的增加以及IFN-γ缺陷型移植中诱导性较低。我们鉴定出40个转录本，它们对IFN-γ具有高度诱导性（例如Cxcl9、泛素D、MHC），以及168个在正常肾脏中对IFN-γ敏感性较低的转录本。在同种异体移植中，GRITs的表达在所有时间点（第3天至42天）都很强烈且一致。这些转录本部分依赖于供体IFN-γ受体（IFN-γRs）：受体缺陷型移植的表达最多降低76%，但有些转录本高度依赖（泛素D），而其他转录本相对独立（Cxcl9）。排斥同种异体移植的宿主肾脏显示出与IFN-γ注射观察到的相似表达。许多GRITs在同基因移植中显示出短暂的IFN-γ依赖性增加，在第4-5天达到峰值。GRITs在心脏同种异体移植中增加，表明它们是同种异体反应的普遍特征。因此，排斥诱导转录本的表达在同种异体移植中是强大且一致的，反映了同种异体反应在局部和全身产生的IFN-γ，通过宿主和供体IFN-γR起作用，以及术后应激诱导的局部IFN-γ产生。
