α4 integrin plays a critical role in early stages of T lymphocyte migration in Peyer's patches of rats

Abstract

Lymphocyte recirculation through the blood flow circuit and lymphoid organs is important for the maintenance of immune defense, and is defined as lymphocyte homing. During the homing process, several adhesion molecules have been postulated to play an important role in lymphocyte recruitment from the vascular space. In the present study, we investigated the effect of a novel mAb against rat α4 integrin (MRα4-1) on the interaction of T lymphocytes with postcapillary venules (PCV) and their subsequent migration into the interstitium of Peyer's patches, using intravital video microscopy. T lymphocytes collected from intestinal lymph were labeled with a fluorochrome carboxyfluorescein diacetate succinimidyl ester and were then injected into the jugular vein of recipient rats. The microvasculature in the ileal Peyer's patches of recipient rats was observed sequentially by intravital fluorescence microscopy. In controls, lymphocytes exhibited rolling behavior which was followed by firm adhesion to the endothelium of PCV. The density of sticking lymphocytes gradually increased during the first 30 min. These initial interactions of lymphocytes with the PCV (rolling and adherence) were drastically inhibited by treatment with MRα4-1, both when MRα4-1 was preinfused into rats and when T cells were preincubated in vitro with MRα4-1 before administration, MRα4-1 also significantly inhibited the transendothelial migration of T lymphocytes, assessed by the ratio of migration to adherence. However, once T lymphocytes migrated into the interstitium, treatment with MRα4-1 did not affect the pattern of travel of these lymphocytes in the interstitium or their transport into the microlymphatics in the parafollicular area. Therefore, we conclude that α4 integrins play a critical role in the rolling and sticking of T cells and their transendothelial migration in PCV of Peyer's patches.