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말초혈액 CD4+CD25- T 세포로부터 IL-4로 유도된 CD4+CD25+ 면역조절 T 세포의 획득과 특성 규명
허성범 ( Seong Beom Heo ),조미라 ( Mi La Cho ),박미경 ( Mi Kyung Park ),민소연 ( So Youn Min ),주지현 ( Ji Hyun Joo ),박경수 ( Kyung Soo Park ),조영규 ( Young Kyu Cho ),윤종현 ( Chong Hyeon Yoon ),박성환 ( Sung Hwan Park ),김호연 대한류마티스학회 2005 대한류마티스학회지 Vol.12 No.4
Objective: The CD4+CD25+ regulatory T cells (Treg) can be induced by TGFβ and IL-10 in the periphery, and understanding the biological function of cytokine-induced Treg is critically important for the control of autoimmune diseases. We investigated the IL-4-induced CD4+CD25+ regulatory T cells in human PBMCs, which were derived from the CD4+CD25- T cells. Methods: The CD4+CD25- T cells from human PBMC were isolated by MACS and cultured in the presence of IL-4 or absence of IL-4. The presence and phenotype of induced CD4+CD25+ T cells were determined by flow cytometry. Supressive activity of induced CD4+CD25+ T cells were assessed by culturing CD4+CD25- and CD4+CD25+ T cells with anti-CD3 monoclonal antibodies and antigen-presenting cells, followed by proliferation. Results: After 5 days, significant amount of CD4+CD25+ T cells were generated from the CD4+CD25- T cells cultured with anti-CD3 antibody in the presence of IL-4. These IL-4 induced CD4+CD25+ T cells presented with similar phenotype to natural occurred Treg cells, including CD45ROhi, CD45RAlo, CTLA-4hi, OX40hi, CD62Lhi and HLA-DRhi, and also exhibited high expression of Foxp3 molecule. In addition, the IL-4 induced CD4+CD25+ T cells can suppress the proliferative responses against anti-CD3. The regulatory property of IL-4 induced CD4+CD25+ T cell was partially abrogated after treatment with anti-IL-10 and anti-TGFβ antibodies. Conclusion: These data indicate that IL-4 induced CD4+CD25+ Treg cells can be generated from the CD4+CD25- T cells in the peripheral blood, and may contribute to the important immunoregulatory function in human.