Hidalgo L G, Einecke G, Allanach K, Halloran P F
Division of Nephrology & Immunology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Am J Transplant. 2008 Mar;8(3):627-36. doi: 10.1111/j.1600-6143.2007.02128.x.
Transcripts expressed in cytotoxic T lymphocytes (CTL) have mechanistic and diagnostic importance in transplantation. We used microarrays to select CTL-associated transcripts (CATs) expressed in human CD4(+) CTL, CD8(+) CTL and NK cells, excluding transcripts expressed in B cells, monocytes and kidney. This generated three transcript sets: CD4(+)-associated, CD8(+)-associated and NK-associated. Surprisingly, many CATs were expressed in effector memory cells e.g. granzyme B/GZMB, interferon-gamma/IFNG. Transcript expression was very similar between CD4(+) and CD8(+) CTL. There were no transcripts highly selective for CD4(+) CTL or CD8(+) CTL: for example, cytotoxic molecule transcripts (perforin, granzymes, granulysin) were shared between CD8(+) CTL and CD4(+) CTL although expression remained higher in CD8(+) CTL. Transcripts that differentiated between CD8(+) CTL and CD4(+) CTL were primarily those shared between CD8(+) CTL and NK cells (e.g. NK receptors KLRC1, KLRC3, KLRD1, KLRK1). No transcripts could differentiate CD4(+) CTL from CD8(+) CTL but NK cell-associated transcripts could differentiate NK cells from CTL. This study serves as a foundation for the interpretation of CATs in rejecting allografts and highlights the extensive sharing of CATs among CD4(+) CTL, CD8(+) CTL and effector memory T cells.
细胞毒性T淋巴细胞（CTL）中表达的转录本在移植中具有机制和诊断意义。我们使用微阵列来选择在人CD4(+) CTL、CD8(+) CTL和NK细胞中表达的CTL相关转录本（CAT），排除在B细胞、单核细胞和肾脏中表达的转录本。这产生了三个转录本组：CD4(+)相关、CD8(+)相关和NK相关。令人惊讶的是，许多CAT在效应记忆细胞中表达，例如颗粒酶B/GZMB、干扰素-γ/IFNG。CD4(+)和CD8(+) CTL之间的转录本表达非常相似。没有对CD4(+) CTL或CD8(+) CTL具有高度选择性的转录本：例如，细胞毒性分子转录本（穿孔素、颗粒酶、颗粒溶素）在CD8(+) CTL和CD4(+) CTL之间共享，尽管在CD8(+) CTL中的表达仍然更高。区分CD8(+) CTL和CD4(+) CTL的转录本主要是CD8(+) CTL和NK细胞之间共享的那些（例如NK受体KLRC1、KLRC3、KLRD1、KLRK1）。没有转录本可以区分CD4(+) CTL和CD8(+) CTL，但NK细胞相关转录本可以区分NK细胞和CTL。这项研究为解释移植排斥反应中的CAT奠定了基础，并强调了CAT在CD4(+) CTL、CD8(+) CTL和效应记忆T细胞之间的广泛共享。
