Cutting edge: Highly alloreactive dual TCR T cells play a dominant role in graft-versus-host disease.

Cutting edge: Highly alloreactive dual TCR T cells play a dominant role in graft-versus-host disease.
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DOI:
10.4049/jimmunol.0900638
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发表时间:
2009-06-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Allen PM
Allen PM
中科院分区:
其他
文献类型:
--
作者:
Morris GP;Allen PM

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同种异体反应性是 T 细胞对胸腺发育过程中未遇到的 MHC 分子的反应。由于 TCRα 的不完全等位基因排除,小鼠和人类中一小部分 (1-8%) 的外周 T 细胞表达两种 TCR,我们假设它们具有高度同种异体反应性。小鼠 T 细胞 MLR 的 FACS 分析显示,同种异体反应细胞中的双 TCR T 细胞有所增加。对同种异体反应库的定量评估表明,在无法表达次级 TCR 的 T 细胞中,同种异体反应性 T 细胞频率减少了近 50%。我们通过鉴定对每个 TCR 具有不同同种异体反应性的双 TCR T 细胞,直接证明了单细胞水平上同种异体反应性 T 细胞库的扩展。双 TCR T 细胞的重要性在 GvHD F1 模型的亲本中得到了清楚的证明,其中双 TCR T 细胞占外周活化 T 细胞的 60%,表明对疾病的贡献不成比例。
Alloreactivity is the response of T cells to MHC molecules not encountered during thymic development. A small population (1–8%) of peripheral T cells in mice and humans express two TCR due to incomplete allelic exclusion of TCRα, and we hypothesized they are highly alloreactive. FACS analysis of mouse T cell MLR revealed increased dual TCR T cells amongst alloreactive cells. Quantitative assessment of the alloreactive repertoire demonstrated a nearly 50% reduction in alloreactive T cell frequency amongst T cells incapable of expressing secondary TCR. We directly demonstrated expansion of the alloreactive T cell repertoire at the single cell level by identifying a dual TCR T cell with distinct alloreactivities for each TCR. The importance of dual TCR T cells is clearly demonstrated in a parent into F1 model of GvHD, where dual TCR T cells comprised up to 60% of peripheral activated T cells, demonstrating a disproportionate contribution to disease.
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