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Molecular effects to human regulatory T cells by treatment with T cell activation inhibitor and TNF blockade
Author(s) -
Suzuki Katsuya,
Setoyama Yumiko,
Suzuki Miyuki,
Keiko Yoshimoto,
Kameda Hideto,
Tsuzaka Kensei,
Amano Koichi,
Takeuchi Tsutomu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1073.10
Subject(s) - foxp3 , il 2 receptor , t cell , flow cytometry , immunology , interleukin 7 receptor , cd3 , cd28 , biology , immune system , pharmacology , cd8
Objective: Regulatory T cell (Treg) has a critical role for human autoimmunity. However, it has not been known how clinically effective therapeutic agents for autoimmune diseases, such as T cell activation inhibitor and TNF blockade affect to Treg in molecular level. Methods: Human CD4+T cells were purified and then co‐cultured with these agents (tacrolimus or infliximab) under anti‐CD3/CD28 antibody stimulation. The cells were harvested and FOXP3+Tregs and its related molecules were analyzed by flow cytometry. Next, DNA microarray analysis of CD4+CD25+CD127‐Treg by in vitro treatment was performed. Results: Tacrolimus significantly reduced CD62L low expressed inducible Tregs in dose dependent manner. In DNA microarray analysis, we have identified significantly up and down regulated 1,021 (tacrolimus) and 621 (infliximab) genes. Gene ontology analysis has also revealed significantly affected 15 gene groups, such as multicellular organismal process in both treatments. Conclusions: Immunological therapeutic intervention obviously affects to human peripheral Tregs in vitro. Its clinical significance should be required further studies in vivo.