Open AccessEffects of interferon‐gamma and tumour necrosis factor‐alpha on the development of cytotoxic T lymphocytes in autologous mixed lymphocyte tumour cultures with human melanoma
Author(s) -
ROTH A. D.,
HORNICEK F. J.,
GERSTNER C. G.,
KIRKWOOD J. M.
Publication year - 1991
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1991.tb05790.x
Subject(s) - cytotoxic t cell , immunology , interferon gamma , melanoma , immunotherapy , tumor necrosis factor alpha , alpha interferon , lymphocyte , t lymphocyte , biology , medicine , cytokine , interferon , cancer research , pathology , immune system , in vitro , biochemistry
SUMMARY We have studied the influence of tumour necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ) on the development of cytotoxic T lymphocytes (CTL) against melanoma in mixed lymphocyte tumour cultures (MLTC). In these MLTC, TNF‐α at 10 4 U/ml increased the expansion of the CTL up to 10 4 ‐fold over recornbinant IL‐2(rIL‐2) alone. IFN‐γ at 10 4 U/ml and combinations of TNF‐α plus IFN‐γ at 10 2 ‐10 3 U/ml promoted the proliferation more variably. MLTC generated with rIL‐2 showed a predominance of CD8 + cells, while 2 weeks of culture in the presence of IFN‐γ at 10 4 U/ml, or with IFN‐γ and TNFα at 1 ± 10 2 ‐10 3 U/ml, favoured the emergence of CD4 + cell populations. The cytotoxic activity of the lymphocytes generated in these MLTC showed a consistent decline of K562 cytotoxic activity following exposure to the combination of IFN‐γ and TNF‐α. Despite the altered T cell subset distribution with different combinations of cytokines. no consistent alteration in the specific anti‐tumour cytotoxicity against melanoma was detected. These results suggest that TNF‐α and IFN‐γ influence the activation, phenolypic. and functional outcome of MLTC‐generated CTL, and may account for the phenotypic variations observed in T cell populations generated in vitro .