APCs in the Anterior Uveal Tract Do Not Migrate to Draining Lymph Nodes

Dullforce, Per; Garman, Kiera L.; Seitz, Greg W.; Fleischmann, Ross J.; Crespo, Sergio M.; Planck, Stephen R.; Parker, David C.; Rosenbaum, James T.

doi:10.4049/jimmunol.172.11.6701

Cited by 45 publications

(51 citation statements)

References 44 publications

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“…Interestingly, a similar situation has been observed in the anterior chamber of the eye, which is another "immune-priviliged" site [35]. Local phagocytic cells ingested fluorescent latex beads after injection in the anterior chamber of the eye and the dermis of the ear pinna.…”

Section: Fluid Routesupporting

confidence: 52%

“…However labeled uveal phagocytes did not migrate to regional lymph nodes, unlike their dermal counterparts. On the other hand, injection of soluble fluorescent ovalbumin in the anterior chamber resulted in its appearance in the draining lymph nodes [35]. Similar experiments in the brain will reinforce the dichotomy between the cellular and fluid routes of antigen access to the peripheral immune system, which is likely to be the strongest determinant of "immune privilege".…”

Section: Fluid Routementioning

confidence: 69%

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What is the blood–brain barrier (not)?

Bechmann

Galea

Perry

2007

Trends in Immunology

467

383

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(preferred mode of contact) This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. The immune privilege of the central nervous system is indispensable for damage limitation during inflammation in a sensitive organ with poor regenerative capacity.It is a longstanding notion which has down the years acquired a lack of precision in its definition and a number of misconceptions. In this article we address these issues and re-define CNS immune privilege in the light of recent data. We show how it is far from absolute and how it varies with age and brain region. Immune privilege in the CNS is often mis-attributed wholly to the blood-brain barrier. We discuss the pivotal role of the specialization of the brain's afferent arm in adaptive immunity, which results in a lack of cell-mediated antigen drainage to the cervical lymph nodes although soluble drainage to these nodes is well described. It is now increasingly recognized how immune privilege is actively maintained as a result of the immunoregulatory characteristics of the CNS resident cells and their microenvironment. Immune privilege down the agesPrivilege: "a right, advantage, or immunity granted to or enjoyed by a person, or class of persons, beyond the common advantages of others" [1].The concept of "immune privilege" in the central nervous system (CNS) has a long history. That antigens trapped within the brain parenchyma evade systemic immunological recognition has been shown as early as 1921 in Japan. Back then, Y Shirai observed that rat sarcoma grew well when transplanted into the mouse brain parenchyma, but not when implanted subcutaneously or intramuscularly [2]. Murphy and Strum extended these findings in 1923 by demonstrating that if recipient spleen was cotransplanted with the foreign tumour in the brain parenchyma, it inhibited the tumour growth [3]. This showed that the survival of the foreign tumour within the brain parenchyma was occurring as a result of disconnection from the systemic immune system. These were the first indications of what was later to be termed "immunological privilege" by Billingham and Boswell [4]. Over the years, these observations have been shown to hold true for tissue grafts [5], bacteria [6], viruses [7] and vectors [8], which all evaded immune recognition when delivered to the brain parenchyma. Around the same time as the brain's "immune privilege" was being discovered, the blood-brain barrier (BBB) was under study, and the two concepts grew together. This had two consequences.First, the brain's "immune privilege" assumed a more absolute meaning, rendering it too strong a descriptive term for the brain's relationship with the immune system (Box 1).Secondly, "immune privilege" was inappropriately wholly attributed to the BBB (see previous article), whereas other features such as the specialization of afferent communication from CNS to nearby lymphatic organs and the nature of the CNS microenvironment are much more pertinent (Box 1). In this article, we aim to upd...

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Section: Fluid Routesupporting

confidence: 52%

Section: Fluid Routementioning

confidence: 69%

What is the blood–brain barrier (not)?

Bechmann

Galea

Perry

2007

Trends in Immunology

467

383

View full text Add to dashboard Cite

show abstract

“…As we previously reported, the APCs labeled by ingestion of fluorescent OVA or BSA are relatively stationary [25]. In marked contrast, many of the T cells are seen migrating within the iris stroma.…”

Section: Resultssupporting

confidence: 52%

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Rosenbaum

Ronick

Song

et al. 2008

Clinical Immunology

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Videomicroscopy is being used increasingly to characterize the interaction of T cells and antigenpresenting cells (APCs) within lymphatic tissues but has not been reported, to our knowledge, at sites of inflammation. We employed intravital videomicroscopy to study an anterior uveitis model using DO11.10 T cells and ovalbumin (OVA). T cell movement in iris was consistent with a random walk independent of the presence of recognized antigen and had a lateral speed slower than T cells in lymph node. Lingering of T cells adjacent to APCs suggested that they were physically interacting. This apparent contact demonstrated antigen specificity when comparing results from DO11.10 cells with OVA versus bovine serum albumin (BSA) loaded APCs but not when comparing results from OVA-loaded APCs with DO11.10 versus HA clonotype 6.5 T cells. Further studies with this model system should clarify the contribution of T cell-APC communication at a site of inflammation, infection, or immunization.

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“…From there, aqueous humor may access the lymphatic vessels draining the loose subconjunctival connective tissue [29][30][31][32][33] . Consequently, molecules injected into the anterior chamber of the eye are partly drained via this pathway and reach the ipsilateral draining cervical LN [23,[34][35][36][37][38][39] .…”

Section: Discussionmentioning

confidence: 99%

Drainage of Fluorescent Liposomes from the Vitreous to Cervical Lymph Nodes via Conjunctival Lymphatics

Camelo¹,

Lajavardi²,

Bochot

et al. 2008

Ophthalmic Res

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The use of liposomes as carriers for the delivery of biologically active molecules into the eye is of major interest. Indeed, encapsulation of biologically active molecules in liposomes may increase their bioavailability and may induce a sustained release, thus avoiding repeated intraocular injections and reducing side effects. We describe here the fate of rhodamine-conjugated liposomes (Rh-Lip) injected into the vitreous of normal Lewis rats. Twenty-four hours after intravitreal injection fluorescent liposomes were detected in the vitreous, the inner layer of the retina and to a lesser extent in the anterior segment of the eye. In addition, numerous Rh-Lip were also observed in the episclera and conjunctival stroma, in conjunctival lymphatic vessels and cervical lymph nodes (LN) draining the conjunctiva and the eye. In the LN, Rh-Lip were taken up by resident macrophages adjacent to CD4+ and CD8+ T cells. Thus, intravitreal injection of anti-inflammatory drugs loaded in liposomes could modulate the ocular immune microenvironment. In addition the passage of drugs into the cervical LN could alter the immune status of these LN and contribute to the regulation of intraocular inflammation. Our results suggest that this phenomenon should be taken into account to design new therapies based on intraocular drug administration.

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APCs in the Anterior Uveal Tract Do Not Migrate to Draining Lymph Nodes

Cited by 45 publications

References 44 publications

What is the blood–brain barrier (not)?

What is the blood–brain barrier (not)?

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Drainage of Fluorescent Liposomes from the Vitreous to Cervical Lymph Nodes via Conjunctival Lymphatics

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