Mobley J L, Dailey M O
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242.
J Immunol. 1992 Apr 15;148(8):2348-56.
A variety of adhesion molecules regulate the traffic and tissue localization of lymphocytes in vivo by mediating their binding to vascular endothelial cells. The homing receptor gp90MEL-14 (gp90), also known as LECAM-1 or L-selectin, mediates the adhesion of lymphocytes to specialized high endothelial venules in lymph nodes (LN) and is the primary molecule regulating lymphocyte recirculation and homing to LN, whereas other adhesion molecules have a major role in the localization of lymphocytes in inflammatory sites. We used four-color flow cytometric analysis to examine the regulation of adhesion receptor expression on LN CD8 T cells responding to skin allografts in vivo. In normal mice, greater than 95% of LN CD8 T cells are gp90+, being either gp90+Pgp1- (Population (Pop.) 1 or gp90+Pgp-1+ (Pop.2). Allografting induces the down-regulation of gp90 and up-regulation of Pgp-1 on a subset of cells, resulting in the appearance of CD8+gp90-Pgp-1hi (Pop. 3) cells. Pop. 3 cells also express high levels of LFA-1, ICAM-1, and ICAM-2, and a subset of them are VLA-4 alpha-positive. Purified Pop. 3 cells have potent cytolytic activity directed against donor alloantigen, whereas no such activity is present in Pop. 1 or 2 cells. Correlating with this is the high granzyme activity in Pop. 3 cells. In addition, Pop. 3 lymphocytes, but not Pop. 1 or 2, secrete a large amount of IFN-gamma in response to Ag. Finally, the CD8 T cells that infiltrate sponge matrix allografts are markedly enriched for the Pop. 3 subset. These results show that, during the immune response to alloantigen in vivo, a small subset of CD8 T cells down-regulates the LN homing receptor while increasing the expression of other adhesion molecules, as they differentiate into highly active cytolytic T lymphocytes. Thus, the differential regulation of LN homing receptors and receptors for peripheral vascular endothelium provides a mechanism that would redirect the traffic of activated effector cells away from lymphoid tissue and to sites of Ag deposition, where they would participate in the inflammatory response.
多种黏附分子通过介导淋巴细胞与血管内皮细胞的结合来调节其在体内的运输和组织定位。归巢受体gp90MEL-14（gp90），也称为LECAM-1或L-选择素，介导淋巴细胞与淋巴结（LN）中特化的高内皮微静脉的黏附，是调节淋巴细胞再循环和归巢至LN的主要分子，而其他黏附分子在淋巴细胞在炎症部位的定位中起主要作用。我们使用四色流式细胞术分析来检测体内对皮肤同种异体移植产生反应的LN CD8 T细胞上黏附受体表达的调节。在正常小鼠中，超过95%的LN CD8 T细胞为gp90阳性，要么是gp90+Pgp1-（群体（Pop.）1），要么是gp90+Pgp-1+（Pop.2）。同种异体移植诱导一部分细胞上gp90下调和Pgp-1上调，导致出现CD8+gp90-Pgp-1hi（Pop. 3）细胞。Pop. 3细胞还高水平表达LFA-1、ICAM-1和ICAM-2，其中一部分是VLA-4α阳性。纯化的Pop. 3细胞对供体同种异体抗原有强大的细胞溶解活性，而Pop. 1或2细胞则没有这种活性。与此相关的是Pop. 3细胞中高颗粒酶活性。此外，Pop. 3淋巴细胞，而不是Pop. 1或2，在接触抗原后分泌大量IFN-γ。最后，浸润海绵基质同种异体移植的CD8 T细胞中Pop. 3亚群明显富集。这些结果表明，在体内对同种异体抗原的免疫反应过程中，一小部分CD8 T细胞在分化为高活性细胞溶解T淋巴细胞时，下调LN归巢受体，同时增加其他黏附分子的表达。因此LN归巢受体和外周血管内皮细胞受体的差异调节提供了一种机制，可将活化的效应细胞的运输从淋巴组织重定向至抗原沉积部位，在那里它们将参与炎症反应。
