Although it is clear that the function of CD40 on peripheral hematopoietic cells is pivotal to the development of autoimmunity, the function of CD40 in autoimmune disease outside this compartment is unresolved. In a model of experimental autoimmune encephalomyelitis (EAE), evidence is presented that CD40–CD154 interactions within the central nervous system (CNS) are critical determinants of disease development and progression. Using bone marrow (BM) chimeric mice, the data suggest that the lack of expression of CD40 by CNS-resident cells diminishes the intensity and duration of myelin oligodendrocyte glycoprotein (MOG)-induced EAE and also reduces the degree of inflammatory cell infiltrates into the CNS. Although CNS inflammation is compromised in the CD40+/+→CD40−/− BM chimeric mice, the restricted CD40 expression had no impact on peripheral T cell priming or recall responses. Analysis of RNA expression levels within the CNS demonstrated that encephalitogenic T cells, which entered a CNS environment in which CD40 was absent from parenchymal microglia, could not elicit the expression of chemokines within the CNS. These data provide evidence that CD40 functions outside of the systemic immune compartment to amplify organ-specific autoimmunity.
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16 April 2001
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April 16 2001
The Clinical Course of Experimental Autoimmune Encephalomyelitis and Inflammation Is Controlled by the Expression of Cd40 within the Central Nervous System
Burkhard Becher,
Burkhard Becher
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
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Brigit G. Durell,
Brigit G. Durell
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
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Amy V. Miga,
Amy V. Miga
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
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William F. Hickey,
William F. Hickey
bDepartment of Pathology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
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Randolph J. Noelle
Randolph J. Noelle
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
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Burkhard Becher
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
Brigit G. Durell
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
Amy V. Miga
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
William F. Hickey
bDepartment of Pathology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
Randolph J. Noelle
aDepartment of Microbiology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03755
Abbreviations used in this paper: BM, bone marrow; BSS, balanced salt solution; CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; H, hamster; MOG, myelin oligodendrocyte glycoprotein; PLP, myelin proteolipid protein.
Received:
November 30 2000
Revision Requested:
February 02 2001
Accepted:
March 14 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 193 (8): 967–974.
Article history
Received:
November 30 2000
Revision Requested:
February 02 2001
Accepted:
March 14 2001
Citation
Burkhard Becher, Brigit G. Durell, Amy V. Miga, William F. Hickey, Randolph J. Noelle; The Clinical Course of Experimental Autoimmune Encephalomyelitis and Inflammation Is Controlled by the Expression of Cd40 within the Central Nervous System. J Exp Med 16 April 2001; 193 (8): 967–974. doi: https://doi.org/10.1084/jem.193.8.967
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