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移植物抗宿主病中CD4⁺和CD8⁺T淋巴细胞上CD43糖型的差异调节

Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease.

作者信息

Ellies L G, Jones A T, Williams M J, Ziltener H J

机构信息

Biomedical Research Centre, University of British Columbia, Vancouver, Canada.

出版信息

Glycobiology. 1994 Dec;4(6):885-93. doi: 10.1093/glycob/4.6.885.

DOI:10.1093/glycob/4.6.885
PMID:7537557
Abstract

Two distinct T-cell glycoforms of CD43 result from differential glycosylation of a single gene product in vivo. The 115 kDa glycoform carries mainly tetrasaccharides and is a pan T-cell marker, whereas the 130 kDa glycoform carries mainly hexasaccharides and is associated with T-cell activation. CD43 has been shown to play a role both in enhancing and inhibiting cell adhesion; however, the function of the individual glycoforms is unknown. We have examined the distribution and regulation of the CD43 glycoforms in a murine model of acute graft-versus-host disease (GVHD) using monoclonal antibodies (mAbs) S7 and 1B11 specific for the 115 and 130 kDa CD43 glycoforms, respectively. An increase in T-lymphocyte CD43 130 kDa expression occurred during GVHD from day 4 onwards and coincided with splenomegaly and upregulation of the beta 1-6GlcNAc transferase (C2GnT), the key enzyme responsible for the addition of complex O-glycan branching to CD43. When T-lymphocyte subsets were examined for CD43 expression, we found that in GVHD, both CD43 glycoforms were upregulated on CD4+ T cells. However, in CD8+ T cells, CD43 115 kDa was downregulated while CD43 130 kDa was dramatically upregulated, such that two distinct CD8+1B11+ T-cell subsets were observed. These data demonstrate differential expression of the CD43 glycoforms in both resting and activated CD4+ and CD8+ T cells, and suggest that glycosylation differences between the CD43 glycoforms may reflect participation in the different functions of these T-cell subsets in immune disorders in vivo.

摘要

体内单一基因产物的差异糖基化产生了两种不同的CD43 T细胞糖型。115 kDa糖型主要携带四糖,是一种泛T细胞标志物,而130 kDa糖型主要携带六糖,与T细胞活化相关。已证明CD43在增强和抑制细胞黏附中均发挥作用;然而,单个糖型的功能尚不清楚。我们使用分别针对115 kDa和130 kDa CD43糖型的单克隆抗体(mAb)S7和1B11,在急性移植物抗宿主病(GVHD)小鼠模型中研究了CD43糖型的分布和调控。从第4天起,GVHD期间T淋巴细胞CD43 130 kDa表达增加,与脾肿大以及β1-6GlcNAc转移酶(C2GnT)上调同时出现,C2GnT是负责向CD43添加复杂O-聚糖分支的关键酶。当检测T淋巴细胞亚群的CD43表达时,我们发现在GVHD中,两种CD43糖型在CD4 + T细胞上均上调。然而,在CD8 + T细胞中,CD43 115 kDa下调,而CD43 130 kDa显著上调,从而观察到两个不同的CD8 + 1B11 + T细胞亚群。这些数据证明了CD43糖型在静息和活化的CD4 +和CD8 + T细胞中的差异表达,并表明CD43糖型之间的糖基化差异可能反映了它们在体内免疫紊乱中参与这些T细胞亚群的不同功能。

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Immunology. 2019 May;157(1):52-69. doi: 10.1111/imm.13047. Epub 2019 Feb 17.
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