Down-regulation of homing receptors after T cell activation.
Down-regulation of homing receptors after T cell activation.
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DOI：
10.4049/jimmunol.141.12.4110
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发表时间：
1988-12
影响因子：
4.4
通讯作者：
T. M. Jung;W. Gallatin;I. Weissman;M. Dailey
中科院分区：
文献类型：
--
作者：
T. M. Jung;W. Gallatin;I. Weissman;M. Dailey
淋巴细胞定位和再循环的特定模式对于正常免疫反应的诱导和表达很重要。为了归巢于淋巴结 (LN)，淋巴细胞必须首先识别并结合 LN 中特定的高内皮小静脉 (HEV)。与 LN HEV 的结合是由特定的淋巴细胞受体介导的，称为归巢受体，可被 mAb MEL-14 识别。我们检查了小鼠 T 淋巴细胞体外激活后归巢受体表达发生的变化。 MLC 或 Con A 激活的细胞识别 HEV 的能力下降 75%，体外与 HEV 结合的减少就证明了这一点。通过淘析器离心从原代 MLC 中分离出的大的活化细胞完全无法识别 HEV，而同一培养物中的小细胞则继续良好地结合。 MEL-14 的流式细胞术分析表明，活化的部分失去了归巢受体 Ag gp90MEL-14 的表达，而失活的细胞仍保持 MEL-14+。随着归巢受体表达的丧失，大多数激活的细胞变成花生凝集素（PNA）强阳性，表明表面糖基化发生显着变化。因此，这些MLC由两个主要的T细胞群组成——小的、失活的淋巴细胞，即MEL-14+PNAlo，和大的、活化的母细胞，即MEL-14-PNAhi。 Con A 激活的纯化 MEL-14+ T 细胞产生 MEL-14- 后代，表明 gp90MEL-14 是从 gp90MEL-14 阳性前体细胞中丢失的，而不是从 MEL-14- 细胞的选择性生长中丢失的。此外，至少一些活化细胞上 Ag 表达的丧失在静息培养中是可逆的，几乎一半的细胞在刺激停止后恢复为 MEL-14+。这些实验表明，T 细胞的激活导致表面归巢受体的下调，导致它们无法识别并结合 HEV 的内皮表面。这表明体内 T 细胞的激活将导致其迁移和定位特性发生显着且生理上显着的变化，这在正常免疫反应期间非常重要。
The specific pattern of lymphocyte localization and recirculation is important for the induction and expression of normal immune responses. In order to home to lymph nodes (LN), lymphocytes must first recognize and bind to specific high endothelial venules (HEV) in the LN. Binding to LN HEV is mediated by specific lymphocyte receptors, termed homing receptors, which are recognized by the mAb MEL-14. We examined the changes that occur in homing receptor expression after activation of murine T lymphocytes in vitro. Cells activated in MLC or by Con A undergo a 75% loss in their ability to recognize HEV, as demonstrated by a decrease in binding to HEV in vitro. Large, activated cells isolated from a primary MLC by elutriator centrifugation were completely unable to recognize HEV, whereas the small cells in the same culture continued to bind well. Flow cytometric analysis with MEL-14 showed that the activated fraction had lost expression of gp90MEL-14, the homing receptor Ag, whereas the inactivated cells remained MEL-14+. Concomitant with the loss of homing receptor expression, most of the activated cells became strongly peanut agglutinin (PNA)-positive, demonstrating a marked change in surface glycosylation. Thus, these MLC consist of two major populations of T cells--small, inactivated lymphocytes that are MEL-14+PNAlo and large, activated blast cells that are MEL-14-PNAhi. Purified MEL-14+ T cells activated by Con A gave rise to MEL-14- progeny, showing that gp90MEL-14 is lost from gp90MEL-14-positive precursors, rather than from the selective growth of MEL-14- cells. Furthermore, the loss of Ag expression on at least some activated cells is reversible in resting culture, with almost half of the cells reverting to MEL-14+ after the cessation of stimulation. These experiments show that activation of T cells results in down-regulation of surface homing receptors, resulting in their inability to recognize and bind to the endothelial surface of HEV. This suggests that the activation of T cells in vivo would result in a dramatic and physiologically significant change in their migration and localization properties which would be important during a normal immune response.