Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex ''re-presentation'' of exogenous antigen by tumor-infiltrating antigen-presenting cells

被引:66
|
作者
Pulaski, BA
Yeh, KY
Shastri, N
Maltby, KM
Penney, DP
Lord, EM
Frelinger, JG
机构
[1] UNIV ROCHESTER,SCH MED & DENT,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642
[2] UNIV ROCHESTER,CTR CANC,PROGRAM IMMUNOL,ROCHESTER,NY 14642
[3] UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720
关键词
D O I
10.1073/pnas.93.8.3669
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-2(d)) 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-2(b) and implanting the tumors in (BALB/c x C57BL/6)F-1 (H-2(d/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.
引用
收藏
页码:3669 / 3674
页数:6
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