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The mode of lymphocyte transendothelial migration in the postcapillary high endothelial venules (HEVs) of Peyer's patches during normal homing and acute inflammation in the guinea pig was studied. It is common opinion that the lymphocyte transendothelial passage from the blood stream into the extravasal lymphoid tissue calls for a multistep process of endothelial and lymphocyte molecules favoring tethering, rolling, activation, arrest and its firm adhesion to the endothelial luminal surface. Ultrastructural serial pictures and the three-dimensional reconstruction of HEVs with lymphocytes during different moments of their transmigration through the endothelial wall enabled us to demonstrate in vivo the morphological modality of their extravasation in lymphoid tissue. The latter is accomplished by means of an intraendothelial canalicular formation (6.8-7.2 microm long and 2.1-2.2 microm in diameter), whose creation depends on the particular behavior of adjacent endothelial cells, without compromising the interendothelial contacts. This new canalicular pathway of lymphocyte extravasation, particularly selective for the B cell, does not permit confirmation of the dogmas of the transcellular and paracellular (open interendothelial junctions) modes that have prevailed in recent decades. The lack of knowledge regarding the molecular bases that would induce constitution of this intraendothelial canalicular formation is a critical point for stimulating future interdisciplinary research aimed at developing strategies for modulating normal lymphocyte homing and in inflammation.

Corrosion casts from neoprene direct injection of lymphatic and blood vessels in guinea pig gut-associated lymphoid tissue, that is, solitary lymphoid follicles and Peyer's patches, have shown both their numerical density and their topographical arrangement in physiological conditions, after starvation and lymphatic stasis. The absorbing peripheral lymphatic vessel (ALPA) begins with the lacteal vessel, which continues in the mucosal lymphatic network. The latter is formed by subepithelial and interfollicular vessels wrapping single lymphoid follicles like a basket. Interfollicular vessels drain in the submucosal network, which flows into muscular tunica vessels with nonsegmentary bicuspid valves. They in turn drain lymph in subserosal precollectors and then in prelymphonodal collectors with conduction function. The follicles' germinal center and dome are completely devoid of ALPA vessels, while they are rich in blood vessels. Ultrastructurally, the ALPA vessel wall consists of a monolayer of endothelial cells devoid of pores, fenestrations, and open junctions and lacking a continuous basal lamina. Endothelial cells are joined by overlapping and interdigitating intercellular contacts, while end-to-end contacts are rare. They have a sizeable cell body, containing the nucleus and the common endocytoplasmic organelles, and a peripheral cytoplasm with actin-like filament bundles, free microvesicles or forming channels and a few rough-surfaced encloplasmic reticulum (RER) canaliculi. The presence of intraendothelial channels crossed by lymphocytes can often be detected within the endothelial wall during the different phases of cell transendothelial migration from lymphoid tissue to lymphatic vessel lumen. These channels undergo a numerical increase during starvation, while they are scarce during lymphatic stasis. We have quantitatively evaluated the prevalence of T lymphocytes in the lymph of interfollicular ALPA vessels and of prelymphonodal collectors draining the small intestine tract with or without Peyer's patches, under physiological and experimental conditions (starvation, lymphatic stasis).

We studied the absorbing lymphatic peripheral vessels of the Peyer's patches of the small and large intestine of the rabbit by means of light microscopy after injection of Neoprene latex and transmission electron microscopy in order to highlight their topographical distributions to blood vessels as well as the morphologic mechanism of transendothelial passage of the lymphocytes to the lymph. The distribution of absorbing lymphatic vessels originates from the lacteal vessels and the subepithelial mucosal lymphatic network, which continue without interruptions and dilations into the vessels of the interfollicular area which are woven into basket-like networks entwining the medio-basal portion of each lymphoid follicle. The interfollicular area vessels then drain into the large vessels of the tunica submucosa, which in turn drain into the valved precollector vessels of the subserosa by way of intramuscular vessels. TEM revealed the absorbing lymphatic vessels to have a continuous endothelial wall without open junctions, fenestrations, and continuous basal lamina. We observed many lymphocytes wedged in the lymphatic endothelial wall. This underlines the different phases of their migration from the lymphoid tissue in the lumen of the lymphatic vessel. Results of ultrathin serial sections and three dimensional reconstruction of lymphatic vessel segments with included lymphocyte showed the transendothelial passage of lymphocyte, through the "intraendothelial channels.", (Copyright 2000 Wiley-Liss, Inc.)