Garrigan K, Moroni-Rawson P, McMurray C, Hermans I, Abernethy N, Watson J, Ronchese F
Malaghan Institute of Medical Research, Wellington South, New Zealand.
Blood. 1996 Nov 1;88(9):3508-12.
We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and present soluble antigen and stimulate major histocompatibility complex (MHC) Class II-restricted T cells. DC from spleen or BM cultures were equally able to stimulate the in vitro proliferation of allogeneic T cells or of antigen-specific T-cell receptor (TCR)-transgenic T cells. Both DC populations also induced comparable levels of IL-2 secretion by a T-cell hybridoma. Therefore, splenic and BM-derived DC express comparable levels of (Antigen + MHC Class II) ligands and/or costimulatory molecules and have comparable ability to stimulate T-cell responses. When presentation of a native protein antigen, rather than peptide, was evaluated, BM-derived DC were at least 50 times better than splenic DC at stimulating the proliferation of TCR-transgenic T cells. The antigen processing ability of the two populations was similar only when splenic DC were used immediately ex vivo. Therefore, unlike spleen DC, BM-derived DC maintain the capacity to process protein antigen for MHC Class II presentation during in vitro culture. Due to these characteristics, BM-derived DC may represent a useful tool in immunotherapy studies, as they combine high T-cell stimulatory properties with the capacity to process and present native antigen.
我们比较了从小鼠脾脏分离的树突状细胞(DC),或由在粒细胞巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)中培养的骨髓(BM)前体细胞在体外生成的DC,它们处理和呈递可溶性抗原以及刺激主要组织相容性复合体(MHC)II类限制性T细胞的能力。来自脾脏或BM培养物的DC同样能够刺激同种异体T细胞或抗原特异性T细胞受体(TCR)转基因T细胞的体外增殖。这两种DC群体还诱导T细胞杂交瘤分泌相当水平的IL-2。因此,脾脏和BM来源的DC表达相当水平的(抗原+MHC II类)配体和/或共刺激分子,并且具有相当的刺激T细胞反应的能力。当评估天然蛋白质抗原而非肽的呈递时,BM来源的DC在刺激TCR转基因T细胞增殖方面比脾脏DC至少强50倍。仅当立即将脾脏DC用于体外实验时,这两种群体的抗原处理能力才相似。因此,与脾脏DC不同,BM来源的DC在体外培养期间保持处理蛋白质抗原以进行MHC II类呈递的能力。由于这些特性,BM来源的DC可能代表免疫治疗研究中的一种有用工具,因为它们兼具高T细胞刺激特性以及处理和呈递天然抗原的能力。