Sato K, Nagayama H, Tadokoro K, Juji T, Takahashi T A
Department of Cell Processing, The Institute of Medical Science, The University of Tokyo, Japan.
Exp Hematol. 1999 Feb;27(2):326-36. doi: 10.1016/s0301-472x(98)00046-0.
Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are required for the initiation of the immune response. DCs have been shown to be generated from hematopoietic stem cells, but relatively little is known about the regulation underlying differentiation and activation of DCs. Here, we report that recombinant human (rh)IL-13 induces functional maturation of rhGM-CSF plus rhIL-4 generated monocyte-derived immature DCs. Incubation of these immature DCs with rhIL-13 or rhTNF-alpha for 2 days resulted in increased surface expression of CD1a, CD11c, CD86 and HLA-DR. The DCs treated with rhIL-13 or rhTNF-alpha, but not rhIL-4, for 2 days were more efficient than unstimulated DCs in the primary autologous/allogeneic T-cell response whereas the antigen (Ag)-specific T-cell response was suppressed. The treatment of DCs with rhIL-13 as well as rhTNF-alpha for 4 days down-modulated endocytic capacity for FITC-dextran (FITC-DX) and lucifer yellow (LY), and induced surface expression of CD83. Morphological, phenotypical, and functional analyses revealed that the monocytes cultured with rhGM-CSF plus rhIL-13 gave rise to a DC type more mature than rhGM-CSF plus rhIL-4-induced DCs. These findings revealed a new role for rhIL-13 in regulating both the maturation and activation of DCs.
树突状细胞(DCs)是启动免疫反应所必需的专职抗原呈递细胞(APCs)。已证明DCs由造血干细胞生成,但关于DCs分化和激活的潜在调控机制知之甚少。在此,我们报告重组人(rh)IL-13可诱导由rhGM-CSF加rhIL-4生成的单核细胞来源的未成熟DCs发生功能成熟。将这些未成熟DCs与rhIL-13或rhTNF-α孵育2天,导致CD1a、CD11c、CD86和HLA-DR的表面表达增加。用rhIL-13或rhTNF-α而非rhIL-4处理2天的DCs在原发性自体/同种异体T细胞反应中比未刺激的DCs更有效,而抗原(Ag)特异性T细胞反应受到抑制。用rhIL-13以及rhTNF-α处理DCs 4天可下调对异硫氰酸荧光素-葡聚糖(FITC-DX)和路西法黄(LY)的内吞能力,并诱导CD83的表面表达。形态学、表型和功能分析表明,用rhGM-CSF加rhIL-13培养的单核细胞产生的DC类型比rhGM-CSF加rhIL-4诱导的DCs更成熟。这些发现揭示了rhIL-13在调节DCs成熟和激活方面的新作用。