Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis.

Shohreh Issazadeh-Navikas; K Abdallah; T Chitnis; A Chandraker; A D Wells; L A Turka; M H Sayegh; S J Khoury

doi:10.1172/JCI8607

Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis.

Shohreh Issazadeh-Navikas, K Abdallah, T Chitnis, A Chandraker, A D Wells, L A Turka, M H Sayegh, S J Khoury

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

35 Citationer (Scopus)

Abstract

Udgivelsesdato: 2000-Apr

Originalsprog	Engelsk
Tidsskrift	Journal of Clinical Investigation
Vol/bind	105
Udgave nummer	8
Sider (fra-til)	1109-16
Antal sider	7
ISSN	0021-9738
DOI	https://doi.org/10.1172/JCI8607
Status	Udgivet - 2000

Bibliografisk note

Keywords: Amino Acid Sequence; Animals; Apoptosis; Cells, Cultured; Central Nervous System; Chronic Disease; Demyelinating Diseases; Disease Susceptibility; Encephalomyelitis, Autoimmune, Experimental; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Myelin-Associated Glycoprotein; Proto-Oncogene Proteins c-bcl-2; T-Lymphocytes; bcl-X Protein

Adgang til dokumentet

10.1172/JCI8607

Citationsformater

@article{94eef27057ce11dd8d9f000ea68e967b,

title = "Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis.",

abstract = "The mechanisms of chronic disease and recovery from relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, are unknown. Deletion of myelin-specific lymphocytes by apoptosis may play a role in termination of the inflammatory response. One pathway of apoptosis is the passive cell death or {"}cell death by neglect{"} pathway, which is under the control of the Bcl family of genes. To investigate the role of passive cell death pathway in EAE, we used mice with transgenic expression of the long form of the bcl-x gene (Bcl-x(L)) targeted to the T-cell lineage. We found that mice transgenic for Bcl-x(L) have an earlier onset and a more chronic form of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 compared with wild-type littermate mice. This was not due to an expanded autoreactive cell repertoire. Primed peripheral lymphocytes from Bcl-x(L) transgenic mice showed increased proliferation and cytokine production to MOG peptide in vitro compared with lymphocytes from wild-type animals. Immunohistologic studies demonstrated increased cellular infiltrates, immunoglobulin precipitation, and demyelination in the Bcl-x(L) transgenic central nervous system (CNS) compared with controls. There was also a decreased number of apoptotic cells in the CNS of Bcl-x(L) transgenic mice when compared with littermates at all time points tested. This is the first report of an autoimmune disease model in Bcl-x(L) transgenic mice. Our data indicate that the passive cell death pathway is important in the pathogenesis of chronic EAE. These findings have implications for understanding the pathogenesis of multiple sclerosis and other autoimmune diseases.",

author = "Shohreh Issazadeh-Navikas and K Abdallah and T Chitnis and A Chandraker and Wells, {A D} and Turka, {L A} and Sayegh, {M H} and Khoury, {S J}",

note = "Keywords: Amino Acid Sequence; Animals; Apoptosis; Cells, Cultured; Central Nervous System; Chronic Disease; Demyelinating Diseases; Disease Susceptibility; Encephalomyelitis, Autoimmune, Experimental; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Myelin-Associated Glycoprotein; Proto-Oncogene Proteins c-bcl-2; T-Lymphocytes; bcl-X Protein",

year = "2000",

doi = "10.1172/JCI8607",

language = "English",

volume = "105",

pages = "1109--16",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "8",

}

TY - JOUR

T1 - Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis.

AU - Issazadeh-Navikas, Shohreh

AU - Abdallah, K

AU - Chitnis, T

AU - Chandraker, A

AU - Wells, A D

AU - Turka, L A

AU - Sayegh, M H

AU - Khoury, S J

N1 - Keywords: Amino Acid Sequence; Animals; Apoptosis; Cells, Cultured; Central Nervous System; Chronic Disease; Demyelinating Diseases; Disease Susceptibility; Encephalomyelitis, Autoimmune, Experimental; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Myelin-Associated Glycoprotein; Proto-Oncogene Proteins c-bcl-2; T-Lymphocytes; bcl-X Protein

PY - 2000

Y1 - 2000

N2 - The mechanisms of chronic disease and recovery from relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, are unknown. Deletion of myelin-specific lymphocytes by apoptosis may play a role in termination of the inflammatory response. One pathway of apoptosis is the passive cell death or "cell death by neglect" pathway, which is under the control of the Bcl family of genes. To investigate the role of passive cell death pathway in EAE, we used mice with transgenic expression of the long form of the bcl-x gene (Bcl-x(L)) targeted to the T-cell lineage. We found that mice transgenic for Bcl-x(L) have an earlier onset and a more chronic form of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 compared with wild-type littermate mice. This was not due to an expanded autoreactive cell repertoire. Primed peripheral lymphocytes from Bcl-x(L) transgenic mice showed increased proliferation and cytokine production to MOG peptide in vitro compared with lymphocytes from wild-type animals. Immunohistologic studies demonstrated increased cellular infiltrates, immunoglobulin precipitation, and demyelination in the Bcl-x(L) transgenic central nervous system (CNS) compared with controls. There was also a decreased number of apoptotic cells in the CNS of Bcl-x(L) transgenic mice when compared with littermates at all time points tested. This is the first report of an autoimmune disease model in Bcl-x(L) transgenic mice. Our data indicate that the passive cell death pathway is important in the pathogenesis of chronic EAE. These findings have implications for understanding the pathogenesis of multiple sclerosis and other autoimmune diseases.

AB - The mechanisms of chronic disease and recovery from relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, are unknown. Deletion of myelin-specific lymphocytes by apoptosis may play a role in termination of the inflammatory response. One pathway of apoptosis is the passive cell death or "cell death by neglect" pathway, which is under the control of the Bcl family of genes. To investigate the role of passive cell death pathway in EAE, we used mice with transgenic expression of the long form of the bcl-x gene (Bcl-x(L)) targeted to the T-cell lineage. We found that mice transgenic for Bcl-x(L) have an earlier onset and a more chronic form of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 compared with wild-type littermate mice. This was not due to an expanded autoreactive cell repertoire. Primed peripheral lymphocytes from Bcl-x(L) transgenic mice showed increased proliferation and cytokine production to MOG peptide in vitro compared with lymphocytes from wild-type animals. Immunohistologic studies demonstrated increased cellular infiltrates, immunoglobulin precipitation, and demyelination in the Bcl-x(L) transgenic central nervous system (CNS) compared with controls. There was also a decreased number of apoptotic cells in the CNS of Bcl-x(L) transgenic mice when compared with littermates at all time points tested. This is the first report of an autoimmune disease model in Bcl-x(L) transgenic mice. Our data indicate that the passive cell death pathway is important in the pathogenesis of chronic EAE. These findings have implications for understanding the pathogenesis of multiple sclerosis and other autoimmune diseases.

U2 - 10.1172/JCI8607

DO - 10.1172/JCI8607

M3 - Journal article

C2 - 10772655

VL - 105

SP - 1109

EP - 1116

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 8

ER -