Jung T M, Gallatin W M, Weissman I L, Dailey M O
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242.
J Immunol. 1988 Dec 15;141(12):4110-7.
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.
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至关重要。为了归巢至淋巴结（LN），淋巴细胞必须首先识别并结合LN中的特定高内皮微静脉（HEV）。与LN HEV的结合由特定的淋巴细胞受体介导，称为归巢受体，可被单克隆抗体MEL-14识别。我们研究了体外激活小鼠T淋巴细胞后归巢受体表达的变化。如体外与HEV结合减少所示，在混合淋巴细胞培养（MLC）中或通过刀豆蛋白A（Con A）激活的细胞识别HEV的能力丧失了75%。通过淘洗离心从初次MLC中分离出的大的、活化的细胞完全无法识别HEV，而同一培养物中的小细胞仍能很好地结合。用MEL-14进行的流式细胞术分析表明，活化部分失去了归巢受体抗原gp90MEL-14的表达，而未活化细胞仍为MEL-14阳性。伴随归巢受体表达的丧失，大多数活化细胞变为强花生凝集素（PNA）阳性，表明表面糖基化发生了显著变化。因此，这些MLC由两个主要的T细胞群体组成——小的、未活化的淋巴细胞，它们是MEL-14+PNAlo，以及大的、活化的母细胞，它们是MEL-14-PNAhi。用Con A激活的纯化MEL-14+T细胞产生了MEL-14-子代，表明gp90MEL-14从gp90MEL-14阳性前体细胞中丢失，而不是来自MEL-14-细胞的选择性生长。此外，至少一些活化细胞上抗原表达的丧失在静止培养中是可逆的，在刺激停止后，几乎一半的细胞恢复为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著且具有生理意义的变化，这在正常免疫反应中很重要。
