Leukocyte infiltration and glial reactions in xenografts of mouse brain tissue undergoing rejection in the adult rat brain. A light and electron microscopical immunocytochemical study

Finsen, Bente; Sørensen, Torben; Castellano, Bernardo; Pedersen, Erik B.; Zimmer, Jens

doi:10.1016/0165-5728(91)90008-u

Cited by 101 publications

(39 citation statements)

References 74 publications

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“…Diverse changes in gene expression patterns in reactive microglia have also been reported (Streit et al, 1988;Kreutzberg, 1996). The labeling of nucleoside diphosphatase (NDPase; Finsen et al, 1991) and OX42 was rapidly increased in reactive microglia following transient cerebral ischemia. After injection of kainate into the brain, major histocompatibility complex class I (MHC class I; OX18) antigen was widely expressed in reactive microglia, while MHC class II (OX6) and leukocyte common antigen (LCA) were seen only in a restricted subpopulation of microglia .…”

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confidence: 91%

Novel objective classification of reactive microglia following hypoglossal axotomy using hierarchical cluster analysis

Yamada

Jinno

2013

J of Comparative Neurology

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A total of 136 microglia were intracellularly labeled and their morphological features were evaluated by 3D morphometric measurement. According to hierarchical cluster analysis, microglia were objectively categorized into four groups termed types I-IV. The validity of this classification was confirmed by principal component analysis and linear discriminant analysis. Type I microglia were found in sham-operated mice and in mice sacrificed 28 days (D28) after axotomy. The appearance of type I cells was similar to so-called ramified microglia in a resting state. Type II microglia were mainly seen in D14 mice, which exhibited small cell bodies with thin and short processes. Interestingly, none of the already-known morphological types of microglia seemed to be comparable to type II cells. We thus named type II microglia "small ramified" cells. Types III and IV microglia were mainly seen in D3 and D7 mice and their appearances were similar to hypertrophied and bushy cells, respectively. Proliferating cell nuclear antigen (PCNA), a mitosis marker, was almost exclusively expressed in D3 mice. On the other hand, voltage-dependent potassium channels (Kv1.3/1.5), neurotoxicity-related molecules, were most highly expressed in D14 mice. Increased expression of Kv1.3/1.5 in D14 mice was suppressed by minocycline treatment. These findings indicate that type II and III microglia may be involved in neurotoxicity and mitosis, respectively. Type IV microglial cells are assumed to be in the process of losing mitotic activity and gaining neurotoxicity. Our data also suggest that type II microglia can be a potential therapeutic target against neurodegenerative diseases.

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confidence: 91%

Novel objective classification of reactive microglia following hypoglossal axotomy using hierarchical cluster analysis

Yamada

Jinno

2013

J of Comparative Neurology

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“…Also, Shirai's rat sarcoma might have survived well in the brains of his mice since it was neoplastic. We now know that non-tumoral intracerebral xenografts do not survive, although their rejection is delayed [9].…”

Section: Absolute and Relative Immune Privilegementioning

confidence: 99%

What is the blood–brain barrier (not)?

Bechmann

Galea

Perry

2007

Trends in Immunology

466

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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“…Also, Shirai's rat sarcoma [2] might have survived well in the brains of his mice because it was neoplastic. We now know that non-tumoral intracerebral xenografts do not survive, although their rejection is delayed [9].…”

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confidence: 99%