Route of lymphocyte migration through the high endothelial venule (HEV) in human palatine tonsil

Indrasingh, Inbam; Chandi, G.; Vettivel, Selvakumar

doi:10.1016/s0940-9602(02)80040-1

Cited by 20 publications

(18 citation statements)

References 37 publications

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“…While some of these studies suggested that lymphocytes migrate between 2 adjacent ECs (paracellular migration), 13,31,32 others have claimed that lymphocytes migrate within the EC (transcellular migration), possibly via the formation of transendothelial channels. [33][34][35][36] Our data do not support or reject any of these models and the precise cascade of events leading to the entry of lymphocytes into the HEV pockets remains to be definitely determined.…”

Section: Discussioncontrasting

confidence: 81%

High endothelial venules as traffic control points maintaining lymphocyte population homeostasis in lymph nodes

Mionnet

Sanos

Mondor

et al. 2011

Blood

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Millions of lymphocytes enter and exit mammal lymph nodes (LNs) each day, accessing the parenchyma via high endothelial venules (HEVs) and egressing via lymphatics. Despite this high rate of cellular flux and the many entry and exit sites within a given LN, the number of lymphocytes present in a resting LN is extraordinary stable over time, raising the question of how this steady-state is maintained. Here we have examined the anatomic details of lymphocyte movement in HEVs, finding that HEVs create pockets within which lymphocytes reside for several minutes before entering the LN proper. The function of these pockets was revealed in experiments performed under conditions in which lymphocyte egress from the LN was compromised by any of several approaches. Under such conditions, the HEVs pockets behaved as "waiting areas" in which lymphocytes were held until space was made available to them for entry into the parenchyma.Thus, rather than being simple entry ports, HEVs act as gatekeepers able to stack, hold and grant lymphocytes access to LN parenchyma in proportion to the rate of lymphocyte egress from the LN, enabling the LN to maintain a constant steadystate cellularity while supporting the extensive cellular trafficking necessary for repertoire scanning. (Blood. 2011;118(23): 6115-6122) IntroductionDespite the constant entry and exit of lymphocytes in the noninflamed state, LNs manage to maintain their cellularity over time, indicating the existence of tightly regulated control mechanisms that balance access and egress of cells. 1 Naive lymphocytes enter LNs via HEVs and exit via lymphatic vessels. 2 The number of HEVs and lymphatic exit sites in an individual LN is quite high, with these sites showing substantial topographic separation throughout the LN. This raises the question of how a LN manages lymphocyte traffic at these many dispersed sites to maintain homeostasis, a critical issue because LNs provide key survival signals such as IL-7 and BAFF (B-cell activating factor) to T and B cells, respectively. 3,4 As a resting LN is believed to secrete defined amounts of such survival signals, increases in lymphocyte number beyond that properly supported by the survival factors available could lead to cell death and repertoire contraction. Likewise, too few cells would limit the number of specific cells available at any time for antigen-driven activation, diminishing the efficiency of immune responses. Interestingly, mice grafted with multiple thymi do not harbor massively enlarged LNs despite high numbers of circulating lymphocytes, suggesting that LNs autoregulate the number of cells they house and nourish. 5,6 Altogether, these observations suggest that LNs adapt lymphocyte entry and exit fluxes to constantly host a fixed number of lymphocytes under steady-state conditions. In this study, we investigate this possibility and demonstrate that, in addition of being passive entry doors for lymphocytes, HEVs are traffic control checkpoints able to create "waiting areas" in which lymphocytes accumulate and are hel...

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Section: Discussioncontrasting

confidence: 81%

High endothelial venules as traffic control points maintaining lymphocyte population homeostasis in lymph nodes

Mionnet

Sanos

Mondor

et al. 2011

Blood

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“…Diapedesis in Peyer's patches (in rat, mouse and guinea pig) was seen to occur either by a transcellular pathway exclusively (Azzali et al, 2008;Cho and De Bruyn, 1986) or by concomitant transcellular and paracellular modes (Yamaguchi and Schoefl, 1983). In HEVs of tonsils removed from humans with tonsillitis, HEVs were crossed both paracellularly and transcellularly (Indrasingh et al, 2002). Other studies (not reviewed here) in various secondary lymphoid organs report exclusive use of paracellular diapedesis.…”

Section: Transcellular Diapedesis In Secondary Lymphoid Organsmentioning

confidence: 79%

Mechanisms for transcellular diapedesis: probing and pathfinding by `invadosome-like protrusions'

Carman

2009

Journal of Cell Science

172

171

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Immune-system functions require that blood leukocytes continuously traffic throughout the body and repeatedly cross endothelial barriers (i.e. diapedese) as they enter (intravasate) and exit (extravasate) the circulation. The very earliest studies to characterize diapedesis directly in vivo suggested the coexistence of two distinct migratory pathways of leukocytes: between (paracellular pathway) and directly through (transcellular pathway) individual endothelial cells. In vivo studies over the past 50 years have demonstrated significant use of the transcellular diapedesis pathway in bone marrow, thymus, secondary lymphoid organs, various lymphatic structures and peripheral tissues during inflammation and across the blood-brain barrier and blood-retinal barrier during inflammatory pathology. Recently, the first in vitro reports of transcellular diapedesis have emerged. Together, these in vitro and in vivo observations suggest a model of migratory pathfinding in which dynamic `invadosome-like protrusions' formed by leukocytes have a central role in both identifying and exploiting endothelial locations that are permissive for transcellular diapedesis. Such `probing' activity might have additional roles in this and other settings.

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“…The clear germinal centers indicated that the yak tonsils played an important role in immune responses. Besides, there were several high endothelial veins in the interfollicular areas, which supported active lymphoid cells migrated from peripheral blood to the secondary lymphoid organs (Indrasingh et al ., ), responsible for communication between local systemic and mucosal adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

Yak (Bos grunniens) Tonsils: Morphological Description and Expression of IgA and IgG

Sun

Cui

et al. 2018

The Anatomical Record

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This study aimed to describe the morphology, expression of IgA and IgG in adult yak tonsils. The 12 clinically healthy yak tonsils [3‐ to 6‐year old, n = 12] were examined for morphology using light, and transmission electron microscopes. Expression of IgA and IgG was measured by qRT‐PCR, ELISA, and immunohistochemistry. The results showed that the palatine tonsil, the tonsil of the soft palate, and the lingual tonsil were oropharyngeal tonsils. The stratified squamous epithelia covering them had a thick underlying layer of connective tissue and their crypts were heavily infiltrated by lymphocytes. The pharyngeal tonsil and the tubal tonsil were nasopharyngeal tonsils. The epithelia of them was predominantly pseudostratified columnar ciliary epithelium, which were loosely arranged with a number of desmosomes or intermediate junctions variably connecting them. The expression levels of IgA and IgG mRNA and protein from high to low was in the pharyngeal tonsil, palatine tonsil, tonsil of the soft palate, lingual tonsil, and tubal tonsil, respectively. Interestingly, the expression of IgG was very significantly higher than that of IgA in yak tonsils (P < 0.01). Both the IgA and IgG ASCs were distributed in the subepithelial areas of the non‐reticular crypt epithelium, especially areas of pseudostratified columnar ciliary epithelium, the reticular crypt epithelium, lymphoid follicles, interfollicular areas, and with some of the positive cells aggregating around the glands. The results indicated that the tonsils were not only typical secondary lymphoid organs but also lymphoepithelial structures. IgG could be a significant component of mucosal immune responses in yak tonsils. Anat Rec, 302:999–1009, 2019. © 2018 Wiley Periodicals, Inc.

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Route of lymphocyte migration through the high endothelial venule (HEV) in human palatine tonsil

Cited by 20 publications

References 37 publications

High endothelial venules as traffic control points maintaining lymphocyte population homeostasis in lymph nodes

High endothelial venules as traffic control points maintaining lymphocyte population homeostasis in lymph nodes

Mechanisms for transcellular diapedesis: probing and pathfinding by `invadosome-like protrusions'

Yak (Bos grunniens) Tonsils: Morphological Description and Expression of IgA and IgG

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