Upregulated expression of fibronectin receptors underlines the adhesive capability of thymocytes to thymic epithelial cells during the early stages of differentiation: Lessons from sublethally irradiated mice
Upregulated expression of fibronectin receptors underlines the adhesive capability of thymocytes to thymic epithelial cells during the early stages of differentiation: Lessons from sublethally irradiated mice
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DOI：
10.1182/blood.v93.3.974.403k19_974_990
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发表时间：
1999-02-01
期刊：
影响因子：
20.3
通讯作者：
Savino, W
中科院分区：
文献类型：
--
作者：
Dalmau, SR;Freitas, CS;Savino, W
采用250 cgy的全身γ辐射剂量诱导小鼠胸腺退化，并研究在器官再生过程中出现的不同胸腺细胞亚群中细胞外基质（ECM）受体的表达和功能。在放疗后第2天至第3天检测再生的开始（P-Ir），此时CD3(-)CD25(hi)CD44（+）和CD3(-)CD25(in/hi)CD44（-）细胞的绝对计数显著增加。l -选择素、α 4和α 5整合素链(L-sel(hi) α 4（hi) α 5(hi)）的表达也增强。这种表达模式一直维持到CD4(+)CD8(+) （DP）幼年期。随后，DP以及CD4（+）或CD8（+）单阳性（SP）胸腺细胞(L-sel(in) α 4（in) α 5(in)）中这些ECM受体普遍下调。在一些新近生成的SP细胞中，α 4的表达在α 5链之前下调，而l -选择素在一半更成熟的细胞中上调。α 6整合素链的表达仅在成熟的CD4（+）细胞中下调。重要的是，胸腺细胞中l -选择素和α 4和α 5链的表达增加与其体外胸腺上皮细胞（TEC）的粘附性密切相关。单克隆抗体或多肽阻断实验表明：(1)在胸腺细胞/TEC粘附过程中，α 4整合素靶向的是LDV而不是纤连蛋白IIIC段的REDV细胞粘附基序；(2) α 5整合素的靶点纤维连接蛋白120-kD片段的RGD基序在这种粘附中起次要作用；(3)非整合素受体识别的层粘连蛋白/merosin β 1链的YIGSR细胞附着基序不用于胸腺细胞粘附。总之，我们的研究结果表明，一组上调的受体赋予CD25（+）前体和细胞直到年轻DP阶段具有与胸腺ECM成分相互作用的高能力。(C) 1999年由美国血液病学会出版。
A 250-cGy whole-body gamma-radiation dose was used to induce thymus regression in mice, and to study the expression and function of extracellular matrix (ECM) receptors in distinct thymocyte subsets emerging during repopulation of the organ. The onset of regeneration was detected from day 2 to 3 postirradiation (P-Ir), when a remarkable increase in the absolute counts of CD3(-)CD25(hi)CD44(+) and CD3(-)CD25(in/hi)CD44(-) cells occurred. Enhanced expression of L-selectin, alpha 4, and alpha 5 integrin chains (L-sel(hi) alpha 4(hi) alpha 5(hi)) was also exhibited by these cells. This pattern of expression was maintained until the CD4(+)CD8(+) (DP) young stage was achieved. Afterward, there was a general downregulation of these ECM receptors in DP as well as in CD4(+) or CD8(+) single positive (SP) thymocytes (L-sel(in) alpha 4(in) alpha 5(in)). In some recently generated SP cells, alpha 4 expression was downregulated before the alpha 5 chain, and L-selectin was upregulated in half of more mature cells. The expression of the alpha 6 integrin chain was downregulated only in maturing CD4(+) cells. Importantly, the increased expression of L-selectin and alpha 4 and alpha 5 chains in thymocytes was strongly correlated with their adhesiveness to thymic epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or peptides showed the following: (1) that the LDV rather than the REDV cell attachment motif in the IIIC segment of fibronectin is targeted by the alpha 4 integrin during thymocyte/TEC adhesion; (2) that the RGD motif of the 120-kD fragment of fibronectin, a target for alpha 5 integrin, has a secondary role in this adhesion; and (3) that the YIGSR cell attachment motif of the beta 1 chain of laminin/merosin recognized by a nonintegrin receptor is not used for thymocyte adherence. In conclusion, our results show that an upregulated set of receptors endows CD25(+) precursors and cells up to the young DP stage with a high capability of interacting with thymic ECM components. (C) 1999 by The American Society of Hematology.