Lacave Roger, Masurier Carole, Guigon Martine, Lemoine François M, Klatzmann David, Colombo Bruno M
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, CNRS UMR 7087/UPMC, Hôpital de la Pitié, Paris, France.
Int J Oncol. 2003 Dec;23(6):1747-53.
Conceptually, dendritic cells (DCs) take up and process exogenous antigens that are presented on MHC (major histocompatibility complex) class II molecules to stimulate CD4+ T cells, and present endogenously-produced proteins to CD8+ T cells through an MHC class I-dependent pathway. In this study, we compared the antitumor effects generated in vivo after vaccinations with DCs either loaded with exogenous protein (DCs-exo) or presenting antigens derived from endogenous-synthesized protein (DCs-endo). We used the murine MC26SC31 colon carcinoma cell line expressing on the cell surface the human CD4 (hCD4) molecule as a model tumor-associated antigen (TAA). Bone marrow (BM)-derived DCs-endo were obtained from histocompatible transgenic mice constitutively expressing hCD4; BM-derived DCs-exo were obtained after in vitro loading DCs, from syngenic normal mice, with purified soluble hCD4 protein (shCD4). Altogether, our results show that intravenous (i.v.) administration of DCs-exo and DCs-endo can trigger similar cytotoxic and humoral protecting immune responses against a lethal tumor challenge. hCD4 antigen-specific T cell-mediated cytotoxic immune response was not accompanied by elevated INF-gamma serum levels. This suggests, in the case of DCs-exo, a possible in vivo CTL cross-priming triggering a CD8+ T cell-mediated immune response in the absence of de novo antigen synthesis within the DCs.
从概念上讲，树突状细胞（DCs）摄取并处理外源性抗原，这些抗原呈递在主要组织相容性复合体（MHC）II类分子上以刺激CD4 + T细胞，并通过MHC I类依赖性途径将内源性产生的蛋白质呈递给CD8 + T细胞。在本研究中，我们比较了用负载外源性蛋白质的DCs（DCs-exo）或呈递源自内源性合成蛋白质的抗原的DCs（DCs-endo）进行疫苗接种后在体内产生的抗肿瘤作用。我们使用在细胞表面表达人CD4（hCD4）分子的小鼠MC26SC31结肠癌细胞系作为模型肿瘤相关抗原（TAA）。从组成性表达hCD4的组织相容性转基因小鼠获得骨髓（BM）来源的DCs-endo；从同基因正常小鼠体外负载DCs与纯化的可溶性hCD4蛋白（shCD4）后获得BM来源的DCs-exo。总之，我们的结果表明，静脉内（i.v.）给予DCs-exo和DCs-endo可以引发针对致命肿瘤攻击的类似细胞毒性和体液保护性免疫反应。hCD4抗原特异性T细胞介导的细胞毒性免疫反应并未伴随着血清INF-γ水平的升高。这表明，在DCs-exo的情况下，可能存在体内CTL交叉启动，在DCs内不存在从头抗原合成的情况下引发CD8 + T细胞介导的免疫反应。
