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Inability of interleukin‐12 to modulate T‐helper 0 effectors to T‐helper 1 effectors: a possible distinct subset of T cells
Author(s) -
}$ Hu$^{,
Salgame
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.1365-2567.1999.00745.x
Subject(s) - biology , interleukin 12 , cytotoxic t cell , interleukin 4 , t helper cell , interleukin 21 , effector , t cell , il 2 receptor , cytokine , interferon gamma , microbiology and biotechnology , immunology , immune system , in vitro , genetics
Interleukin‐12 (IL‐12) strongly favours the development of T‐helper 1 (Th1)‐type cells through its ability to induce interferon‐γ (IFN‐γ) production by natural killer cells and T cells. In the present work we analysed the effects of IL‐12 on the synthesis and secretion of IFN‐γ and IL‐4 by human T‐cell clones. Several previously described human T‐cell clones exhibiting Th1, Th2 or Th0 phenotypes were used for these analyses. We demonstrated, by enzyme‐linked immunosorbent assay (ELISA) and intracytoplasmic staining, that, in Th0 clones, IL‐12 up‐regulated the production of both IFN‐γ and IL‐4 and was unable to modulate these cells to Th1‐type. The up‐regulation of cytokine gene expression was transcriptionally regulated and was not due to differences in mRNA stability. In Th1 cells, IL‐12 up‐regulated only IFN‐γ and not IL‐4. However, in Th2 cells, both IFN‐γ and IL‐4 were up‐regulated by IL‐12. This suggests that Th2 cells may be less stable than Th1 cells. We also observed that human Th2 cells expressed the IL‐12β2 receptor, in contrast to murine Th2, which lacks this receptor. The observed differences in the effects of IL‐12 on the three T‐cell subsets may have important ramifications for IL‐12‐based therapies.