Open AccessSuppression of lymphokine‐activated killer (LAK) cell induction mediated by interleukin‐4 and transforming growth factor‐β1: effect of addition of exogenous tumour necrosis factor‐alpha and interferon‐gamma, and measurement of their endogenous production
Author(s) -
BROOKS B,
CHAPMAN K.,
LAWRY J.,
MEAGER A.,
REES R. C.
Publication year - 1990
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.1365-2249.1990.tb05494.x
Subject(s) - lymphokine , lymphokine activated killer cell , tumor necrosis factor alpha , interleukin 2 , cytokine , biology , immunology , interferon gamma , peripheral blood mononuclear cell , transforming growth factor , recombinant dna , natural killer cell , lymphocyte , cytotoxicity , antigen , immune system , endocrinology , t cell , in vitro , interleukin 21 , biochemistry , gene
SUMMARY Recombinant human interleukin‐4 (rhlL‐4) and transforming growth factor‐βl (TGF‐β1) suppressed the induction of lymphokine‐activated killer (LAK) activity induced by recombinant human interleukin‐2 (rhIL‐2) in peripheral blood lymphocytes. DNA synthesis and the expression of the p55 alpha chain of the IL‐2 receptor (Tac antigen) were also inhibited. The inhibitory effect was greatest when these factors were added during the first 48 h of a 4‐day culture, with reduced cytolytic activity against both natural killer (NK) resistant and NK‐sensitive tumour cell line targets. The suppressive action of both cytokines was accompanied by a reduction in tumour necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐ γ ) levels in lymphocyte culture supernatants. Recombinant human IFN‐ γ (rhIFN‐ γ ). but not recombinant human TNF‐α (rhTNF‐α) was able to overcome the inhibitory effect of recombinant human interleukin‐4(rhIL‐4) on LAK induction and DNA synthesis but not Tac antigen expression. However, cytotoxicity induced by rhI FN‐ γ alone was also suppressed by rhIL‐4 and TGF‐β1, inferring that rhIFN‐ γ ‐mediated abrogation of rhlL‐4 suppression was not simply a direct IL‐2‐indcpendent effect on cytotoxicity. In addition, rhIL‐4 did not increase TGF‐β production from rhIL‐2‐activated peripheral blood mononuclear cells, suggesting that rhIL‐4 did not mediate reduction of rhIL‐2 responses through the induction of TGF‐β release.