Pulaski B A, Yeh K Y, Shastri N, Maltby K M, Penney D P, Lord E M, Frelinger J G
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3669-74. doi: 10.1073/pnas.93.8.3669.
We show that interleukin 3 (IL-3) enhances the generation of tumor-specific cytotoxic T lymphocytes (CTLs) through the stimulation of host antigen-presenting cells (APCs). The BALB/c (H-2d) spontaneous lung carcinoma line 1 was modified by gene transfection to express ovalbumin as a nominal "tumor antigen" and to secrete IL-3, a cytokine enhancing myeloid development. IL-3-transfected tumor cells are less tumorigenic than the parental cell line, and tumor-infiltrating lymphocytes isolated from these tumors contain increased numbers of tumor-specific CTLs. By using B3Z86/90.14 (B3Z), a unique T-cell hybridoma system restricted to ovalbumin/H-2b and implanting the tumors in (BALB/c x C57BL/6)F1 (H-2d/b) mice, we demonstrate that the IL-3-transfected tumors contain an increased number of a rare population of host cells that can process and "re-present" tumor antigen to CTLs. Electron microscopy allowed direct visualization of these host APCs, and these studies, along with surface marker phenotyping, indicate that these APCs are macrophage-like. The identification of these cells and their enhancement by IL-3 offers a new opportunity for tumor immunotherapy.
我们发现,白细胞介素3(IL-3)通过刺激宿主抗原呈递细胞(APC)来增强肿瘤特异性细胞毒性T淋巴细胞(CTL)的生成。通过基因转染对BALB/c(H-2d)自发性肺癌细胞系1进行改造,使其表达卵清蛋白作为一种名义上的“肿瘤抗原”,并分泌IL-3,一种促进髓系发育的细胞因子。与亲代细胞系相比,转染IL-3的肿瘤细胞致瘤性较低,从这些肿瘤中分离出的肿瘤浸润淋巴细胞中肿瘤特异性CTL的数量增加。通过使用B3Z86/90.14(B3Z),一种独特的受卵清蛋白/H-2b限制的T细胞杂交瘤系统,并将肿瘤植入(BALB/c×C57BL/6)F1(H-2d/b)小鼠体内,我们证明转染IL-3的肿瘤中含有数量增加的一类罕见宿主细胞,这类细胞能够处理肿瘤抗原并将其“再次呈递”给CTL。电子显微镜能够直接观察到这些宿主APC,这些研究以及表面标志物表型分析表明,这些APC类似巨噬细胞。这些细胞的鉴定及其被IL-3增强为肿瘤免疫治疗提供了新的机会。