Celluzzi C M, Mayordomo J I, Storkus W J, Lotze M T, Falo L D
Department of Dermatology, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
J Exp Med. 1996 Jan 1;183(1):283-7. doi: 10.1084/jem.183.1.283.
Cytotoxic T lymphocytes (CTLs) are a critical component of the immune response to tumors. Tumor-derived peptide antigens targeted by CTLs are being defined for several human tumors and are potential immunogens for the induction of specific antitumor immunity. Dendritic cells (DC) are potent antigen-presenting cells (APCs) capable of priming CTL responses in vivo. Here we show that major histocompatibility complex class I-presented peptide antigen pulsed onto dendritic APCs induces protective immunity to lethal challenge by a tumor transfected with the antigen gene. The immunity is antigen specific, requiring expression of the antigen gene by the tumor target, and is eliminated by in vivo depletion of CD8+ T cells. Furthermore, mice that have rejected the transfected tumor are protected from subsequent challenge with the untransfected parent tumor. These results suggest that immunization strategies using antigen-pulsed DC may be useful for inducing tumor-specific immune responses.
细胞毒性T淋巴细胞(CTLs)是肿瘤免疫反应的关键组成部分。CTLs靶向的肿瘤衍生肽抗原正在被确定用于多种人类肿瘤,并且是诱导特异性抗肿瘤免疫的潜在免疫原。树突状细胞(DC)是强大的抗原呈递细胞(APC),能够在体内引发CTL反应。在这里,我们表明,负载于树突状APC上的主要组织相容性复合体I类呈递肽抗原可诱导针对用该抗原基因转染的肿瘤的致死性攻击的保护性免疫。这种免疫是抗原特异性的,需要肿瘤靶标表达抗原基因,并且通过体内耗竭CD8 + T细胞而消除。此外,已排斥转染肿瘤的小鼠可免受未转染亲本肿瘤的后续攻击。这些结果表明,使用抗原负载的DC的免疫策略可能有助于诱导肿瘤特异性免疫反应。