IL-4 Induces CD4+CD25+ Regulatory T Cells from CD4+CD25- T Cells in Peripheral Blood / 대한류마티스학회지

ABSTRACT

OBJECTIVE: The CD4+CD25+ regulatory T cells (Treg) can be induced by TGFbeta 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 CD45RO(hi), CD45RA(lo), CTLA-4(hi), OX40(hi), CD62L(hi) and HLA-DR(hi), 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-TGFbeta 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.