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Kinetics of cytokine and NFAT gene expression in human interleukin‐2‐dependent T lymphoblasts stimulated via T‐cell receptor
Author(s) -
Timo Sareneva,
Sampsa Matikainen,
J. Vanhatalo,
Krister Melén,
Jukka Pelkonen,
Ikka Julkunen
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00440.x
Subject(s) - biology , microbiology and biotechnology , cytokine , lymphoblast , interleukin 2 , t cell , peripheral blood mononuclear cell , cd3 , cd8 , lymphokine , antigen , immune system , immunology , cell culture , biochemistry , genetics , in vitro
T cells respond to mitogenic or antigenic stimulation by proliferation and by turning on cytokine gene expression. Here we have analysed the kinetics and nature of cytokine production in human peripheral blood‐derived T lymphoblasts stimulated with anti‐CD3 antibodies or Lens culinaris lectin (LCL). T cells were purified from peripheral blood mononuclear cells (PBMC) and primarily activated with anti‐CD3 antibodies and cultured in the presence of interleukin‐2 (IL‐2). Anti‐CD3‐restimulated T cells (mainly CD8 + ) produced IL‐2, interferon‐γ (IFN‐γ) and tumour necrosis factor‐α (TNF‐α) and low levels of IL‐4 and IL‐10 transcripts and proteins. No IL‐6 gene expression was observed. In LCL‐stimulated cells the cytokine production pattern was very similar. Steady‐state mRNA levels of IL‐2, IL‐10 and IFN‐γ peaked at 3 hr after anti‐CD3 stimulation and declined rapidly thereafter. The kinetics of TNF‐α mRNA expression was faster, being at its peak level 1 hr after stimulation. Anti‐CD3‐stimulated IL‐2 gene expression was down‐regulated by protein synthesis inhibitor, whereas IL‐10, IFN‐γ and TNF‐α genes were readily induced independent of ongoing protein synthesis. T‐cell receptor stimulation also induced a very rapid expression of c‐ jun , c‐ fos and NFATc1 (NFATc) genes, the gene products of which are involved in cytokine gene expression. In conclusion, the cytokines synthesized by IL‐2‐dependent T cells were predominantly IL‐2, IFN‐γ and TNF‐α.