TY - JOUR
T1 - Potential environmental and host participants in the early white matter lesion of adreno-leukodystrophy
T2 - Morphologic evidence for CD8 cytotoxic T cells, cytolysis of oligodendrocytes, and CD1-mediated lipid antigen presentation
AU - Ito, Masumi
AU - Blumberg, Benjamin M.
AU - Mock, David J.
AU - Goodman, Andrew D.
AU - Moser, Ann B.
AU - Moser, Hugo W.
AU - Smith, Kirby D.
AU - Powers, James M.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - The 2 most common forms of X-linked adreno-leukodystrophy (ALD) are the juvenile or childhood cerebral form with inflammatory demyelination and the adult adrenomyeloneuropathy (AMN) involving spinal cord tracts without significant inflammation. Modifier genes or environmental factors may contribute to the phenotypic variability. We performed immunohistochemical, an in situ polymerase chain reaction, and TUNEL analyses to identify several viruses, lymphocyte subpopulations, apoptotic cells, and effector molecules, focusing on morphologically normal white matter, dysmyelinative and acute demyelinative lesions. No distinguishing viral antigens were detected. Most lymphocytes were CD8 cytotoxic T cells (CTLs) with the α/β TCR, and they infiltrated morphologically unaffected white matter. Only a few oligodendrocytes were immunoreactive for caspase-3. MHC class II- and TGF-β-positive microglia were present. CD44, which can mediate MHC-unrestricted target cell death, was seen on many lymphocytes and white matter elements. CD1 molecules, which play major roles in MHC-unrestricted lipid antigen presentation, were noted. Our data indicate that unconventional CD8 CTLs are operative in the early stages of dysmyelination/demyelination and that cytolysis of oligodendrocytes, rather than apoptosis, appears to be the major mode of oligodendrocytic death. The presentation of lipid antigens may be a key pathogenetic element in ALD and AMN-ALD.
AB - The 2 most common forms of X-linked adreno-leukodystrophy (ALD) are the juvenile or childhood cerebral form with inflammatory demyelination and the adult adrenomyeloneuropathy (AMN) involving spinal cord tracts without significant inflammation. Modifier genes or environmental factors may contribute to the phenotypic variability. We performed immunohistochemical, an in situ polymerase chain reaction, and TUNEL analyses to identify several viruses, lymphocyte subpopulations, apoptotic cells, and effector molecules, focusing on morphologically normal white matter, dysmyelinative and acute demyelinative lesions. No distinguishing viral antigens were detected. Most lymphocytes were CD8 cytotoxic T cells (CTLs) with the α/β TCR, and they infiltrated morphologically unaffected white matter. Only a few oligodendrocytes were immunoreactive for caspase-3. MHC class II- and TGF-β-positive microglia were present. CD44, which can mediate MHC-unrestricted target cell death, was seen on many lymphocytes and white matter elements. CD1 molecules, which play major roles in MHC-unrestricted lipid antigen presentation, were noted. Our data indicate that unconventional CD8 CTLs are operative in the early stages of dysmyelination/demyelination and that cytolysis of oligodendrocytes, rather than apoptosis, appears to be the major mode of oligodendrocytic death. The presentation of lipid antigens may be a key pathogenetic element in ALD and AMN-ALD.
KW - Adreno-leukodystrophy
KW - CD1
KW - CD44
KW - CD8
KW - Granzyme B
KW - Lipid antigen
KW - Microglia
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U2 - 10.1093/jnen/60.10.1004
DO - 10.1093/jnen/60.10.1004
M3 - Article
C2 - 11589421
AN - SCOPUS:0034810289
VL - 60
SP - 1004
EP - 1019
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
SN - 0022-3069
IS - 10
ER -