Transition from enhanced T cell infiltration to inflammation in the myelin-degenerative central nervous system.
Myelin degeneration in the central nervous system (CNS) is often associated with elevated numbers of T cells in brain and spinal cord (SC). In some degenerative diseases, this T cell immigration has no clinical relevance, in others, it may precede severe inflammation and tissue damage. We studied T cells in the myelin-degenerative SC of transgenic (tg) Lewis rats overexpressing the proteolipid protein (PLP). These lymphocytes are T(H)1/T(C)1 cells and represent different T cell clones unique to individual animals. The SC-infiltrating CD8(+) T cell pool is more restricted than its CD4(+) counterpart, possibly due to constrictions in the peripheral CD8(+) T cell repertoire. Some SC-infiltrating T cells are highly motile and cover large distances within their target tissue, others are tethered to MHC class II(+) microglia cells. The activation of the tethered cells may trigger the formation of inflammatory foci and could pave the way for inflammation in degenerative CNS disease.
Grundtner
Roland
R
Medical University Vienna, Center for Brain Research, Division of Neuroimmunology, Spitalgasse 4, A-1090 Vienna, Austria.
Dornmair
Klaus
K
Dahm
Ralf
R
Flügel
Alexander
A
Kawakami
Naoto
N
Zeitelhofer
Manuel
M
Schoderboeck
Lucia
L
Nosov
Mikhail
M
Selzer
Edgar
E
Willheim
Martin
M
Kiebler
Michael
M
Wekerle
Hartmut
H
Lassmann
Hans
H
Bradl
Monika
M
D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000473:pathology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D013057:Spectrum Analysis; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines; D018991:Myelin Proteolipid Protein; D049452:Green Fluorescent Proteins