Decreased 4-1BB expression on CD4+CD25 high regulatory T cells in peripheral blood of patients with multiple sclerosis.
As a tumour necrosis factor receptor superfamily member, 4-1BB (CD137) is preferentially expressed in CD4+CD25+ regulatory T cells (Tregs) and has been suggested to play an important role in regulating the generation or function of Tregs. Recent studies of human Tregs have shown that blood CD4+CD25(high) T cells were much closer to Tregs in terms of their functionality. Furthermore, CD4+CD25(high) Tregs have been found to have a decreased effector function in patients with multiple sclerosis (MS). In this study, we examined the expression of 4-1BB and soluble 4-1BB (s4-1BB) protein levels in the peripheral blood of MS patients. Compared with healthy controls, MS patients had decreased 4-1BB expression in their CD4+C25(high) Tregs and increased plasma s4-1BB protein levels. Moreover, the plasma s4-1BB levels of MS patients were shown to be inversely correlated with the 4-1BB surface expression of CD4+CD25(high) Tregs. The down-regulated 4-1BB expression on CD4+CD25(high) Tregs of MS patients may be involved in the impaired immunoactivity of these Tregs. The elevated s4-1BB levels may, at least in part, function as a self-regulatory attempt to inhibit antigen-driven proliferation of Tregs or their immunosuppressive activity.
Liu
G-Z
GZ
Department of Neurology, Peking University People's Hospital, Beijing, China. guangzhi@public.bta.net.cn
Gomes
A C
AC
Fang
L-B
LB
Gao
X-G
XG
Hjelmstrom
P
P
D000328:Adult; D000704:Analysis of Variance; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018189:Immunomagnetic Separation; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017634:Self Tolerance; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000032:analysis* / Q000097:blood / Q000235:genetics
D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9