Swainson Louise, Kinet Sandrina, Manel Nicolas, Battini Jean-Luc, Sitbon Marc, Taylor Naomi
Institut de Génétique Moléculaire, Unité Mixte de Recherche 5535, Montpellier, Cedex 5, France.
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12867-72. doi: 10.1073/pnas.0503603102. Epub 2005 Aug 26.
GLUT1, the major glucose transporter in peripheral T lymphocytes, is induced upon T cell receptor activation. However, the role of GLUT1 during human thymocyte differentiation remains to be evaluated. Our identification of GLUT1 as the human T lymphotrophic virus (HTLV) receptor has enabled us to use tagged HTLV-receptor-binding domain fusion proteins to specifically monitor surface GLUT1 expression. Here, we identify a unique subset of CD4+ CD8+ double-positive (DP) thymocytes, based on their GLUT1 surface expression. Whereas these cells express variable levels of CD8, they express uniformly high levels of CD4. Glucose uptake was 7-fold higher in CD4(hi) DP thymocytes than in CD4(lo) DP thymocytes (P = 0.0002). Further analyses indicated that these GLUT1+ thymocytes are early post-beta-selection, as demonstrated by low levels of T cell receptor (TCR)alphabeta and CD3. This population of immature GLUT1+ DP cells is rapidly cycling and can be further distinguished by specific expression of the transferrin receptor. Importantly, the CXCR4 chemokine receptor is expressed at 15-fold higher levels on GLUT1+ DP thymocytes, as compared with the DP GLUT1- subset, and the former cells show enhanced chemotaxis to the CXCR4 ligand CXCL12. Thus, during human thymopoiesis, GLUT1 is up-regulated after beta-selection, and these immature DP cells constitute a population with distinct metabolic and chemotactic properties.
葡萄糖转运蛋白1（GLUT1）是外周T淋巴细胞中的主要葡萄糖转运体，在T细胞受体激活时被诱导。然而，GLUT1在人类胸腺细胞分化过程中的作用仍有待评估。我们将GLUT1鉴定为人嗜T淋巴细胞病毒（HTLV）受体，这使我们能够使用带有标签的HTLV受体结合域融合蛋白来特异性监测GLUT1的表面表达。在此，我们根据GLUT1的表面表达鉴定出CD4⁺CD8⁺双阳性（DP）胸腺细胞的一个独特亚群。这些细胞虽然表达水平各异的CD8，但均一性地高表达CD4。CD4高表达的DP胸腺细胞的葡萄糖摄取量比CD4低表达的DP胸腺细胞高7倍（P = 0.0002）。进一步分析表明，这些GLUT1⁺胸腺细胞处于β选择后的早期阶段，这可通过低水平的T细胞受体（TCR）αβ和CD3得以证明。这群未成熟的GLUT1⁺DP细胞快速增殖，并且可通过转铁蛋白受体的特异性表达进一步区分。重要的是，与DP GLUT1⁻亚群相比，CXCR4趋化因子受体在GLUT1⁺DP胸腺细胞上的表达水平高15倍，并且前者细胞对CXCR4配体CXCL12表现出增强的趋化性。因此，在人类胸腺生成过程中，GLUT1在β选择后上调，并且这些未成熟的DP细胞构成了具有独特代谢和趋化特性的群体。
