Analysis of the effect of cytokines (interleukins 2, 3, 4, and 6, granulocyte-monocyte colony-stimulating factor, and interferon-gamma) on generation of primary cytotoxic T lymphocytes against a weakly immunogenic tumor.
We have investigated the role of cytokines (IL-2, IL-3, IL-4, IL-6, IFN-gamma, and GM-CSF) in the generation of primary cytotoxic T lymphocytes (CTL), within a single tumor system. The murine carcinoma line 1 was transfected with expression vectors with cDNA for these cytokines. Line 1 expresses low levels of class I MHC molecules, but can be induced with dimethyl sulfoxide or IFN-gamma to express high levels of class I. Class I low line 1 cells are not susceptible to CTL lysis, while class I high line 1 are lysed by CTL, which allows us to assay for CTL activity. To isolate primary CTL, tumor-infiltrating lymphocytes were isolated from cytokine-expressing or control tumors, growing in vivo. Most cytokines stimulated nonspecific killers, but IL-2 and IL-3 stimulated primary CTL. While IFN-gamma alone did not generate primary CTL, coexpression of IFN-gamma with IL-2 resulted in CTL generation. This is the first comparison of the effects of a series of cytokines on primary CTL development, and has important implications for vaccine development and immunotherapy.
McAdam
A J
AJ
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Pulaski
B A
BA
Storozynsky
E
E
Yeh
K Y
KY
Sickel
J Z
JZ
Frelinger
J G
JG
Lord
E M
EM
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007371:Interferon-gamma / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007378:Interleukins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor