Yeh K Y, McAdam A J, Pulaski B A, Shastri N, Frelinger J G, Lord E M
Department of Microbiology and Immunology and Cancer Center Immunology Program, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
J Immunol. 1998 Jun 15;160(12):5773-80.
Recent studies have reported that APC can present particulate exogenous Ag in the context of class I MHC to CD8+ CTL, and our laboratory demonstrated that IL-3 could enhance CTL generation to exogenous Ag. In this paper, we wished to determine whether presentation of particulate Ag could be enhanced by IL-3. A T cell hybridoma, B3Z86/90.14 (B3Z) restricted to Ova/Kb, was used as an indicator for presentation of particulate Ag with class I MHC. When activated, this hybridoma expresses lacZ, allowing a simple colorimetric measurement of Ag-specific T cell stimulation. We demonstrated that bone marrow cells stimulated by IL-3 in vivo and in vitro exhibited significantly increased presentation of exogenous OVA linked to beads. Lysate from OVA-transfected line 1 murine lung adenocarcinoma cells (line 1/OVA) was also presented by IL-3-stimulated bone marrow cells, suggesting that these APC can process tumor fragments or debris. Studies using TAP1/2-deficient mice and Ag presentation inhibitors indicate that this exogenous Ag presentation is mediated via the conventional class I MHC pathway. Adoptive transfer of IL-3-stimulated bone marrow cells pulsed with lysate from line 1/OVA tumor cells into naive recipient mice led to the generation of a potent CTL response. These observations indicate that use of such cells may provide a new avenue for development of tumor vaccines.
最近的研究报道,抗原提呈细胞(APC)能够在I类主要组织相容性复合体(MHC)的背景下将颗粒性外源性抗原呈递给CD8⁺细胞毒性T淋巴细胞(CTL),并且我们实验室证实白细胞介素-3(IL-3)能够增强对外源性抗原的CTL生成。在本文中,我们希望确定颗粒性抗原的呈递是否能够被IL-3增强。一种受卵清蛋白/小鼠主要组织相容性复合体I类分子Kb(Ova/Kb)限制的T细胞杂交瘤B3Z86/90.14(B3Z)被用作I类MHC呈递颗粒性抗原的指示物。当被激活时,这种杂交瘤表达β-半乳糖苷酶(lacZ),从而能够通过简单的比色法测量抗原特异性T细胞刺激。我们证实,体内和体外受IL-3刺激的骨髓细胞对外源性与珠子相连的卵清蛋白(OVA)的呈递显著增加。IL-3刺激的骨髓细胞也呈递来自OVA转染的1型小鼠肺腺癌细胞(1/OVA细胞系)的裂解物,这表明这些APC能够处理肿瘤片段或碎片。使用TAP1/2缺陷小鼠和抗原呈递抑制剂的研究表明,这种外源性抗原呈递是通过传统的I类MHC途径介导的。将用1/OVA肿瘤细胞裂解物脉冲处理的IL-3刺激的骨髓细胞过继转移到未致敏的受体小鼠中导致产生有效的CTL反应。这些观察结果表明,使用此类细胞可能为肿瘤疫苗的开发提供一条新途径。