Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells.
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.
Pulaski
B A
BA
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Yeh
K Y
KY
Shastri
N
N
Maltby
K M
KM
Penney
D P
DP
Lord
E M
EM
Frelinger
J G
JG
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000648:ultrastructure; D000951:Antigens, Neoplasm / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006825:Hybridomas; D007167:Immunotherapy; D007377:Interleukin-3 / Q000494:pharmacology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D007377:Interleukin-3; D010047:Ovalbumin