RRC ID 1279
著者 Williams YN, Baba H, Hayashi S, Ikai H, Sugita T, Tanaka S, Miyasaka N, Kubota T.
タイトル Dipeptidyl peptidase IV on activated T cells as a target molecule for therapy of rheumatoid arthritis.
ジャーナル Clin Exp Immunol
Abstract The extracellular domain of the T cell co-stimulatory molecule CD26 possesses dipeptidyl peptidase IV (DP IV) enzyme activity. Activated T cells are known to increase expression of cell surface DP IV and some specific inhibitors of this enzyme have been reported to suppress T cell function. Previously we have identified a DP IV inhibitor, designated TMC-2, found in culture supernatant of Aspergillus oryzae. Administration of TMC-2 to rats with adjuvant arthritis caused marked suppression of paw swelling. To elucidate the mechanism of TMC-2 antiarthritic activity, we have studied its effects on T cell function. Here we show that TMC-2 inhibited DP IV activity of CD26 immunoprecipitated from T cell lysates, and also inhibited proliferative responses of T cells to specific antigen or anti-CD3 antibody. Suppression of IL-2 production was demonstrated at both the mRNA and protein levels. TMC-2 did not alter the PTPase activity of pure CD45, but when this molecule was co-precipitated from T cell lysates together with associated CD26, its PTPase was virtually completely abolished by TMC-2. These results suggest that modulation of CD45 PTPase activity might be responsible for functional suppression of T cells by TMC-2. Because the effects of TMC-2 on T cells were reversible and it was not toxic at the concentrations used, TMC-2 may be a candidate novel therapeutic agent for rheumatoid arthritis.
巻・号 131(1)
ページ 68-74
公開日 2003-1-1
DOI 10.1046/j.1365-2249.2003.02020.x
PII 2020
PMID 12519388
PMC PMC1808610
MeSH Arthritis, Rheumatoid / drug therapy* Arthritis, Rheumatoid / immunology Cell Division / drug effects Cells, Cultured Depression, Chemical Dipeptidyl Peptidase 4* / blood Enzyme Inhibitors / therapeutic use Humans Indoles / therapeutic use* Interleukin-2 / immunology Isoquinolines / therapeutic use* Leukocyte Common Antigens / blood Lymphocyte Activation* T-Lymphocytes / enzymology* T-Lymphocytes / immunology
IF 3.532
引用数 24
WOS 分野 IMMUNOLOGY
リソース情報
ヒト・動物細胞 CCRF-HSB-2(RCB0016)