Premium
IL‐8 induces T cell Chemotaxis, suppresses IL‐4, and up‐regulates IL‐8 production by CD4 + T cells
Author(s) -
Gesser Borbala,
Lund Marianne,
Lohse Nicolai,
Vestergaard Christian,
Matsushima Kouji,
SindetPedersen Steen,
Jensen Steen Lindkaer,
ThestrupPedersen Kristian,
Larsen Christian Grønhøj
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.59.3.407
Subject(s) - microbiology and biotechnology , biology , chemotaxis , cytokine , recombinant dna , cell culture , interleukin 3 , monoclonal antibody , t cell , interleukin 2 , interleukin , antibody , il 2 receptor , immunology , biochemistry , immune system , receptor , gene , genetics
Interleukin‐8 (IL‐8), a neutrophil‐activating cytokine, also activates certain T cell functions such as Chemotaxis. We additionally find ( n = 6) that recombinant (rIL‐8; 1–100 ng/ml), when added to 24 h culture of human CD4 + T cells, suppressed the spontaneous production of IL‐4 (50–85%). Steady state production of IL‐4 was typically around 30 pg/ml, determined by use of a solid‐ phase immunoabsorbant assay. De novo synthesis of IL‐4 from CD4 + T cells cultured for 3 days was also evaluated by use of detection of [ 35 S]methionine incorporation, as visualized by autoradiography of 2‐D gels, and showed that IL‐8 suppressed IL‐4 production. This suppression of IL‐4 production was confirmed in the cytosol fraction by use of Western blotting. The effect of IL‐8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon‐γ, both strongly suppressing IL‐4 production. The regulatory effect of IL‐8 on IL‐4 production was also indicated by the fact that addition of a neutralizing monoclonal anti‐IL‐8 antibody (WS.4) enhanced the spontaneous IL‐4 production when added to the cultures of CD4 + T cells, thereby probably inactivating the effect of IL‐8 originating from the cutured T cells. Also, we observed that IL‐4 mRNA expression was down‐regulated when the CD4 + T cells were cultured for 12 h in the presence of 100 ng/ml IL‐8. The suppression of IL‐4 mRNA expression could be prevented by adding anti‐IL‐8 (20 μg/ml) or IL‐10 (100 ng/ml) 1 h before adding rIL‐8. Thus, IL‐8 may be an important regulator of CD4 + T cell‐derived IL‐4, thereby possibly regulating the balance between humoral and cellular T cell‐dependent responses.