Cytostasis of different tumours by a murine PPD-reactive CD4+ T lymphocyte clone is mediated by interferon-gamma and tumour necrosis factor alone or synergistically.
We have shown that a murine CD4+ PPD-reactive T lymphocyte clone was weakly cytotoxic towards the syngeneic tumour B16 melanoma and MC6A fibrosarcoma which had been coated with PPD using a monoclonal antibody-PPD heteroconjugate. Cell-free supernatants produced by PPD-stimulated T lymphocyte clones were however highly cytostatic for the two tumour targets when assayed over 48-72 h. In this study we have demonstrated good titres of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) in the supernatants, which accounted for their observed cytostatic activity on the tumour targets. The high level of cytostasis seen with the B16 melanoma using the supernatants could be attributed to their sensitivity to the cytostatic activity of IFN-gamma; the lower levels of cytostasis seen with the IFN-gamma-resistant MC6A target was the result of IFN-gamma increasing the sensitivity of this target to TNF. Antibodies to IFN-gamma were able to neutralize the majority of the cytostatic activity of the supernatants on both targets, consistent with the role demonstrated for this lymphokine.
Wing
M G
MG
Molecular Immunopathology Unit, MRC Centre, Cambridge, England.
Montgomery
A M
AM
Harley
C
C
Lachmann
P J
PJ
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D005354:Fibrosarcoma / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014373:Tuberculin / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
D015704:CD4 Antigens; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma