Human oligodendrocytes are susceptible to cytolysis by major histocompatibility complex class I-restricted lymphocytes

Ruijs, Theodora C.G.; Freedman, Mark S.; Grenier, Yannick; Olivier, André; Antel, Jack P.

doi:10.1016/0165-5728(90)90058-u

Cited by 45 publications

(24 citation statements)

References 23 publications

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“…ICAM-1 +/class I1 MHC + astrocytes can function as antigen-presenting cells for the antigen-sensitized T cells (Fontana et al, 1984). ICAM-2 + /class I MHC + oligodendrocytes and ICAM-1 + or ICAM-2 + /class I MHC + astrocytes may become susceptible targets for class I-restricted cytotoxic T cells (Skias et al, 1987;Ruijs et al, 1990). Further studies are needed to evaluate this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes

Satoh¹,

Kim²,

Kastrukoff³

et al. 1991

J of Neuroscience Research

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Expression of intercellular adhesion molecule-1 (ICAM-1), ICAM-2-like molecule (Lgp55), and class I/II major histocompatibility complex (MHC) antigens (H-2 and Ia) was investigated in cultures of murine oligodendrocytes and astrocytes. Under unstimulated conditions, low levels of ICAM-1 expression were observed on astrocytes (less than 20%), but not on oligodendrocytes. Lgp55 was expressed intensely on oligodendrocytes (greater than 90%) and to a lesser degree on astrocytes (greater than 70%). A weak class I MHC (H-2) immunoreactivity was identified on both oligodendrocytes and astrocytes (50-70%). Class II MHC (Ia) antigen was undetectable on both cell types. After 48-hr exposure to immune mediators that include interferon-gamma (IFN-gamma), 500 U/ml, and supernatant from concanavalin A (Con A)-activated spleen cells, ICAM-1 expression was markedly increased on astrocytes (greater than 80%), but not on oligodendrocytes. Lgp55 expression on both cell types was not altered. Induction of H-2 antigen expression by immune mediators was quite high on both cell types (greater than 95%), while Ia antigen induction was low on astrocytes (less than 50%) and did not occur on oligodendrocytes. Cell type-specific expression and induction of ICAMs and MHC antigens by immune mediators may play roles in lymphocyte-glial cell interactions at the sites of inflammation in the central nervous system (CNS).

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Section: Discussionmentioning

confidence: 99%

Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes

Satoh¹,

Kim²,

Kastrukoff³

et al. 1991

J of Neuroscience Research

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“…Macrophages are one of the main cell types inducing oligodendrocyte damage by TNF-a, FasL, ROS/RNS, and other mechanisms. Furthermore, astrocytes were shown to be potentially harmful to oligodendrocytes by mechanisms involving TNF-a, LT, and RNS has been shown that oligodendrocytes are susceptible to cytolysis by CD8 + T lymphocytes (Jurewicz et al 1998;Ruijs et al 1990). Furthermore, an involvement of CD8 + cytotoxic T lymphocytes in autoimmune demyelination was shown in experimental autoimmune encephalomyelitis (EAE) (Huseby et al 2001;Sun et al 2001).…”

Section: Cd8 + T Lymphocytesmentioning

confidence: 99%

Lame Ducks or Fierce Creatures? - The Role of Oligodendrocytes in Multiple Sclerosis

Zeis

Schaeren-Wiemers

2008

J Mol Neurosci

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In the pathogenesis of multiple sclerosis (MS), oligodendrocytes and its myelin sheaths are thought to be the primary target of destruction. The mechanism leading to oligodendrocyte injury and demyelination is still elusive. Oligodendrocytes are maintaining up to 50 internodes of myelin, which is an extraordinary metabolic demand. This makes them one of the most vulnerable cell types in the central nervous system (CNS), and even small insults can lead to oligodendrocyte impairment, demyelination, and axonal dysfunction. For this reason, oligodendrocytes are viewed as more or less the "lame ducks" of the CNS who can easily become victims. However, recent data demonstrate that this perception possibly needs to be revised. The latest data suggest that oligodendrocytes may also act as "fierce creatures," influencing the surrounding cells in many ways to preserve its own, as well as their function, allowing sustained functionality of the CNS upon an attack. In this review, the concept of "reactive or activated oligodendrocyte" is introduced, describing alterations in oligodendrocytes which are either protective mechanisms allowing survival in otherwise lethal environment or influence and possibly modulate the ongoing inflammation. Although "harnessed", oligodendrocytes might actively modulate and shape their environment and be part of the immune privilege of the brain.

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“…In a series of papers from Jack Antel’s laboratory, human oligodendrocytes, cultured from resected tissue from epilepsy patients, were used as targets in assays to assess the capacity of T cells to kill. Major histocompatability (MHC‐I or II)‐unrestricted killing by gamma‐delta T cells or CD4 + T cells was reported [ 5, 59, 184, 158]. The killing was TNFα‐independent; indeed, neither soluble TNFα nor lymphotoxin (LT/TNFα) were lytic in these cultures [ 53, 86].…”

Section: Immunologically Mediated Myelin Damage and Oligodendrocyte Dmentioning

confidence: 99%

“…Ruijs et al . [ 184] have further proposed that human oligodendrocytes are lysed by CD8 + T cells in an MHC‐I‐restricted fashion ( Table 1). Oligodendrocytes are vulnerable to changes in cytosolic calcium [Ca 2+ ] i fluxes induced by the membrane attack complex of complement, or by T cell‐derived perforin in vitro [ 90].…”

Section: Immunologically Mediated Myelin Damage and Oligodendrocyte Dmentioning

confidence: 99%

Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease

Merrill

Scolding

1999

Neuropathology Appl Neurobio

100

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Oligodendrocytes synthesize and maintain myelin in the central nervous system (CNS). Damage may occur to these cells in a number of conditions, including infections, exposure to toxins, injury, degeneration, or autoimmune disease, arising both in the course of human disease and in experimental animal models of demyelination and dysmyelination; multiple sclerosis is the commonest human demyelinating disorder. Conventional classical accounts of the pathology of this and other myelin diseases have given great insights into their core features, but there remain considerable uncertainties concerning the timing, means and cause(s) of oligodendrocyte and myelin damage. At present, therapeutic efforts largely concentrate on immune manipulation and damage limitation, an approach that has produced only modest effects in multiple sclerosis. One reason for this must be the limited understanding of the mechanisms underlying cell damage - clearly, successful therapeutic strategies for preserving the oligodendrocyte-myelin unit must depend on knowledge of how oligodendrocyte damage and death occurs. In this review, mechanisms of oligodendrocyte and myelin damage are considered, and attempts made to relate them to disease processes, clinical and experimental. The hallmarks of different cell death processes are described, and oligodendrocyte-myelin injury by cellular and soluble mediators is discussed, both in vitro and invivo. Recent developments concerning the pathological involvement of oligodendrocytes in neurodegenerative disease are summarized. Finally, these neuropathological and applied neurobiological observations are drawn together in the context of multiple sclerosis.

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Human oligodendrocytes are susceptible to cytolysis by major histocompatibility complex class I-restricted lymphocytes

Cited by 45 publications

References 23 publications

Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes

Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes

Lame Ducks or Fierce Creatures? - The Role of Oligodendrocytes in Multiple Sclerosis

Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease

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