Shankar Gopi, Pestano Linda A, Bosch Marnix L
Northwest Biotherapeutics, Inc, 21720-23rd Dr, SE, Suite 100, Bothell, WA, U,S,A.
J Transl Med. 2003 Oct 10;1(1):7. doi: 10.1186/1479-5876-1-7.
Dendritic cells (DC) are increasingly prepared in vitro for use in immunotherapy trials. Mature DC express high levels of surface molecules needed for T cell activation and are superior at antigen-presentation than immature DC. Bacillus Calmette-Guerin (BCG) is one of several products known to induce DC maturation, and interferon (IFN)-gamma has been shown to enhance the activity of DC stimulated with certain maturation factors. In this study, we investigated the use of IFN-gamma in combination with the powerful maturation agent, BCG. The treatment of immature DC with IFN-gamma plus BCG led to the upregulation of CD54, CD80, and CD86 in comparison with BCG treatment alone. In MLR or recall immune responses, the addition of IFN-gamma at the time of BCG-treatment did not increase the number of antigen-specific T cells but enhanced the development of IFN-gamma-producing Th1 cells. In primary immune responses, on the other hand, BCG and IFN-gamma co-treated DC stimulated higher proportions of specific T cells as well as IFN-gamma secretion by these T cells. Thus the use of IFN-gamma during BCG-induced DC maturation differentially affects the nature of recall versus naïve antigen-specific T-cell responses. IFN-gamma co-treatment with BCG was found to induce IL-12 and, in some instances, inhibit IL-10 secretion by DC. These findings greatly enhance the potential of BCG-matured dendritic cells for use in cancer immunotherapy.
树突状细胞（DC）越来越多地在体外制备，用于免疫治疗试验。成熟的DC表达高水平的T细胞激活所需的表面分子，并且在抗原呈递方面比未成熟的DC更具优势。卡介苗（BCG）是已知可诱导DC成熟的几种产品之一，并且干扰素（IFN）-γ已被证明可增强由某些成熟因子刺激的DC的活性。在本研究中，我们研究了IFN-γ与强大的成熟剂BCG联合使用的情况。与单独使用BCG处理相比，用IFN-γ加BCG处理未成熟的DC导致CD54、CD80和CD86的上调。在混合淋巴细胞反应（MLR）或回忆免疫反应中，在BCG处理时添加IFN-γ并没有增加抗原特异性T细胞的数量，但增强了产生IFN-γ的Th1细胞的发育。另一方面，在初次免疫反应中，BCG和IFN-γ共同处理的DC刺激了更高比例的特异性T细胞以及这些T细胞分泌IFN-γ。因此，在BCG诱导的DC成熟过程中使用IFN-γ对回忆性与幼稚抗原特异性T细胞反应的性质有不同的影响。发现IFN-γ与BCG共同处理可诱导DC分泌IL-12，并且在某些情况下抑制IL-10的分泌。这些发现大大增强了BCG成熟的树突状细胞用于癌症免疫治疗的潜力。
