Defective post-thymic tolerance mechanisms during the chronic progressive stage of multiple sclerosis.
We have recently isolated a panel of T-cell clones from chronic progressive multiple sclerosis (MS) patients that are capable of functioning as antigen-presenting cells and of expressing the costimulatory molecules B7-1 and B7-2. In this report we show that these T-cell clones are resistant to inhibitory regulation, including the induction of anergy and sensitivity to tumor growth factor-beta (TGF-beta)-induced growth inhibition. The resistance to anergy induction was associated with expression of B7 costimulatory molecules. These data suggest that lack of responsiveness to peripheral inhibitory signals may account for the entry of autoimmune diseases into a chronic progressive phase.
Correale
J
J
Department of Neurology, University of Southern California, School of Medicine, Los Angeles 90033, USA.
Gilmore
W
W
Lopez
J
J
Li
S Q
SQ
McMillan
M
M
Weiner
L P
LP
D000328:Adult; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002908:Chronic Disease; D017635:Clonal Anergy; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D007376:Interleukin-2; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma