Lymphatic efflux of intracerebrally injected cells

Oehmichen, M.; Grüninger, H; Wiethölter, H.; Genčić, M.

doi:10.1007/bf00691806

Cited by 47 publications

(24 citation statements)

References 26 publications

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“…on, olfactory nerve. erythrocytes, which primarily drained into cervical lymph nodes [23,24]. Carson et al [25] extended this knowledge to intrathecally injected dendritic cells, and others [26,27] have recently reported similar results.…”

Section: Discussionmentioning

confidence: 70%

T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa

Goldmann

Kwidzinski

Brandt

et al. 2006

Journal of Leukocyte Biology

168

109

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Although drainage pathways of soluble antigens from brain to cervical lymph nodes have been well established, there is no direct evidence for similar routes of leukocytes leaving the central nervous system. We developed a protocol allowing the cross-sectioning of an entire head-neck preparation while preserving the signal of the GFP. We monitored how GFP-expressing CD4 T lymphocytes injected into the entorhinal cortex after lesion or the lateral ventricle of unlesioned C57/bl6 mice reach cervical lymph nodes. Irrespective of the injection site, we demonstrate their passage through the cribroid plate, appearance in the nasal mucosa, and specific accumulation in one of the cervical lymph nodes.

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Section: Discussionmentioning

confidence: 70%

T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa

Goldmann

Kwidzinski

Brandt

et al. 2006

Journal of Leukocyte Biology

168

109

View full text Add to dashboard Cite

show abstract

“…Although macrophages bearing myelin antigens have been described within cervical lymph nodes of monkeys with experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) patients [19], there is no reliable evidence that inflammatory cells bearing CNS antigen migrate out of the CNS parenchyma. When living DCs are injected into the brain parenchyma, they do not emigrate to local lymph nodes [20] but do following ICV injection or if excessively large numbers of cells in large volumes are injected intraparenchymally [21][22][23]. A crucial component for interpreting these experiments is the recognition that the injected volumes must be sufficiently small so as not to overwhelm the limited extracellular volume of the brain parenchyma [24], must avoid the ventricles and meninges, and must limit damage to the brain tissue.…”

Section: Cellular Routementioning

confidence: 99%

What is immune privilege (not)?

Galea

Bechmann

Perry

2007

Trends in Immunology

660

499

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“…When living DCs are injected into the brain parenchyma they do not emigrate to local lymph nodes [20] but do following ICV injection or if excessively large numbers of cells in large volumes are injected intraparenchymally [21,22,23]. A critical component for the interpretation of these experiments is the recognition that the injected volumes must be sufficiently small so as not to overwhelm the limited extracellular volume of the brain parenchyma [24], must avoid the ventricles and meninges, and must limit damage to the brain tissue.…”

Section: Cellular Routementioning

confidence: 99%

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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Lymphatic efflux of intracerebrally injected cells

Cited by 47 publications

References 26 publications

T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa

T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa

What is immune privilege (not)?

What is the blood–brain barrier (not)?

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