The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system

doi:10.1016/0306-4522(96)00160-1

Neuroscience

Volume 74, Issue 2, 19 July 1996, Pages 599-608

https://doi.org/10.1016/0306-4522(96)00160-1 Get rights and content

Abstract

Dendritic cells of the rat were studied immunohistochemically with MRC OX62 monoclonal antibody and using electron microscopy. In normal CNS, a small number of OX62+ cells were detected in the choroid plexus and meninges. These cells were absent from other CNS and peripheral nervous system sites studied. Dendritic cells were also studied in two models of immune-mediated inflammatory conditions in the CNS. These were: acute experimental allergic encephalomyelitis and aberrant delayed-type hypersensitivity lesions induced as a response to heat-killed bacillus Calmette Guérin sequestrated behind the blood–brain barrier. In addition, a group of animals with a delayed-type hypersensitivity response was treated with dexamethasone to assess the effect of steroid treatment on T-cells and OX62+ cells in CNS lesions. Dendritic cells were present in many but not all lesions in acute experimental allergic encephalomyelitis and their numbers were small. In experimental allergic encephalomyelitis lesions, dendritic cells were found predominantly in perivascular cuffs, where they constituted approximately 2% of a total number of major histocompatibility complex class II+ cells. Some of these cells were also detected in the CNS parenchyma, close to the perivascular cuff. In contrast, dendritic cells were present in all delayed-type hypersensitivity lesions studied. Their number in delayed-type hypersensitivity lesions was significantly higher than in experimental allergic encephalomyelitis lesions. Numerous OX62+ cells were found, even in three-month-old lesions. Electron microscopy studies revealed that these cells were often in close contact with lymphocytes. There was no significant change in the density of both OX62+ cells, IL2R+ cells and OX19+ T-cells in delayed-type hypersensitivity lesions after seven-day treatment with dexamethasone, although there was a considerable reduction in the number of CD45RA+ T-cells.

The high numbers of dendritic cells found in the delayed-type hypersensitivity lesions may be important in contributing to the chronicity of the response. They may also initiate autoimmune responses to CNS antigens uncovered during bystander tissue damage which occurs as a consequence of aberrant delayed-type hypersensitivity responses.

Section snippets

Animals

Male Lewis rats, four and eight weeks old, were obtained from Charles River (U.K.). The animals were housed under standard conditions.

Induction of experimental allergic encephalomyelitis

To induce EAE, eight-week-old rats were immunized with 100 μg of MBP prepared as previously described,[7]omitting cation exchange chromatography. MBP was emulsified in complete Freund's adjuvant (containing 1 mg/ml of mycobacterium tuberculosis H37Ra; Sigma, U.K.) and given subcutaneously. Animals were killed on days 5, 7, 9, 10, 11, 12, 15 and 17. At least two

OX62 staining in normal central and peripheral nervous systems

We looked for OX62-positive cells (OX62+) in a number of different sites in the CNS and peripheral nervous system (PNS), and compared the staining of OX62 mAb with that of OX6 mAb. OX62+ cells were absent from most of the PNS and CNS sites studied, including the brain and the spinal cord parenchyma. However, there was a small number of OX62+ cells in the choroid plexus and meninges.

To assess quantitatively the number of OX62+ cells in the choroid plexus, the staining of OX62 was compared to

Discussion

The results show that OX62+ dendritic cells are present in acute EAE lesions as well as in DTH lesions induced in response to BCG sequestrated in the CNS parenchyma. There were more OX62+ dendritic cells in the DTH lesions than in the acute EAE lesions.

Earlier studies have shown that dendritic cells are absent from the normal CNS parenchyma (for review, see [47]), and our present studies confirmed this. We also found that DCs are absent from other CNS and PNS compartments apart from the choroid

Conclusions

Dendritic cells are absent from the normal CNS parenchyma; however, they are present in both acute EAE lesions and the DTH lesions. The number of DCs in DTH lesions is significantly larger than in EAE lesions. Furthermore, in DTH lesions DCs have been found to persists for months. We also found that these cells persist in the CNS lesions after steroid treatment and therefore may be involved in renewing CNS inflammation.

Acknowledgements

This work was supported by The Multiple Sclerosis Society.

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The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system

Abstract

Section snippets

Animals

Induction of experimental allergic encephalomyelitis

OX62 staining in normal central and peripheral nervous systems

Discussion

Conclusions

Acknowledgements

Life Sci.

J. neurol. Sci.

Immunobiology

Immun. Today

Neuroscience

J. Neuroimmun.

Neuroscience

Adv. Immun.

Immun. Today

Molec. Immun.

F4/80, a monoclonal antibody directed specifically against the mouse macrophage

Eur. J. Immun.

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells

J. clin. Invest.

The MRC OX-62 antigen: a useful marker in the purification of rat veiled cells with the biochemical properties of an integrin

J. exp. Med.

Experimental allergic encephalomyelitis: successful treatment in vivo with a monoclonal antibody that recognises T helper cells

J. Immun.

Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells [published erratum appears in Science (1992) 257, (5078): 1848]

Science

Susceptibility of dendritic cells to HIV-1 infection in vitro

J. Leukoc. Biol.

Marked dendritic cell–T cell cluster formation in the pancreatic lymph node of the non-obese diabetic mouse

Immunology

The roles of host and donor cells in the rejection of skin allografts by T cell-deprived rats injected with syngeneic T cells

Eur. J. Immun.

Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes

Ann. Neurol.

Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo

J. exp. Med.

Dendritic cells as antigen presenting cells in vivo

Int. Rev. Immun.

Identification of proliferating dendritic cell precursors in mouse blood

J. exp. Med.

Co-stimulatory functions of antigen presenting cells

J. invest. Dermat.