Abnormal expression of CTLA-4 by T cells from patients with myasthenia gravis: effect of an AT-rich gene sequence.
Cytolytic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in the down-regulation of antigen-activated immune responses. The aberrant CTLA-4 expression is characterized by low surface and intracellular levels of CTLA-4 protein, impaired up-regulation of CTLA-4 in T cells in response to ConA stimulation and high levels of soluble CTLA-4 (sCTLA-4) in serum. The serum levels of sCTLA-4 are positively correlated with the serum concentration of antibodies against the acetylcholine receptor. The (AT)(n) polymorphism in the 3'-untranslated region contributes to decreased mRNA stability and, hence, to reduced expression of CTLA-4.
Wang
Xiong-Biao
XB
Immunological Research Unit, Department of Medicine, Center for Molecular Medicine (CMM) L8: 03, Karolinska Institutet, Karolinska Hospital, S-17176, Stockholm, Sweden.
Kakoulidou
Maria
M
Giscombe
Ricardo
R
Qiu
Qianhui
Q
Huang
DeRen
D
Pirskanen
Ritva
R
Lefvert
Ann Kari
AK
D020856:AT Rich Sequence / Q000235:genetics*; D000069594:Abatacept; D000328:Adult; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003208:Concanavalin A; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D003208:Concanavalin A; D000069594:Abatacept; D004247:DNA