Premium
Interleukin‐15 differentially enhances the expression of interferon‐γ and interleukin‐4 in activated human (CD4 + ) T lymphocytes
Author(s) -
Pieter Borger,
Hf Kauffman,
Dirkje S. Postma,
Mt Esselink,
Edo Vellenga
Publication year - 1999
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.1365-2567.1999.00679.x
Subject(s) - cd28 , downregulation and upregulation , biology , interleukin 4 , microbiology and biotechnology , interleukin 2 , interferon gamma , cd3 , cytokine , concanavalin a , cd8 , immune system , immunology , in vitro , biochemistry , gene
In this study interleukin (IL)‐15 was examined for its ability to modulate the expression of interferon‐γ (IFN‐γ) and IL‐4 in activated human T lymphocytes. The effect of IL‐15 was compared with IL‐2 and IL‐7, cytokines all known to use the IL‐2 receptor γ C chain. The results demonstrate that the extent of upregulation of IFN‐γ and IL‐4 mRNA was dependent on the applied cytokine (IL‐2>IL‐15>IL‐7) and on the stimulatory signal. IFN‐γ and IL‐4 mRNAs were upregulated by IL‐15 in concanavalin A‐ (twofold) and anti‐CD3 plus anti‐CD28‐ (fivefold) stimulated T lymphocytes. IFN‐γ mRNA accumulation, but not IL‐4 mRNA, was additively upregulated by IL‐15 plus IL‐7 (ninefold) in anti‐CD3 stimulated T lymphocytes, and bypassed the requirement of CD28 signalling. Fluorescence‐activated cell sorting (FACS) experiments demonstrated that IFN‐γ mRNA was upregulated by IL‐15 in both CD4 + and CD8 + T lymphocytes, whereas IL‐4 mRNA accumulation predominantly occurred in CD4 + cells. Preincubation of highly purified CD4 + T lymphocytes during 7 days with IL‐15 and/or IL‐7, followed by activation, also showed enhanced IL‐4 protein secretion, but predominantly upregulated IFN‐γ protein. The net effect was a dramatically increased IFN‐γ/IL‐4 ratio. Taken together, IL‐15 and IL‐7 can act as costimulatory signals, which may favour a T helper 1 (Th1) immune response, particularly in the absence of sufficient CD28 costimulation.