Development in vitro of human CD4+ thymocytes into functionally mature Th2 cells. Exogenous interleukin‐12 is required for priming thymocytes to produce both Th1 cytokines and interleukin‐10

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Abstract
Fresh postnatal thymocyte cell suspensions were directly cloned under limiting dilution conditions with either phytohemagglutinin or toxic shock syndrome toxin‐1 (TSST‐1), a bacterial superantigen. Cultures contained allogenic irradiated feeder cells and interleukin (IL)‐2, in the absence or presence of exogenous IL‐4, interferon (IFN)‐γ or IL‐12. The resulting CD4+ T cell clones generated under these different experimental conditions were then analyzed for their ability to produce IL‐2, IL‐4, IL‐5, IL‐10, IFN‐γ and tumor necrosis factor (TNF)‐β in response to stimulation with phorbol 12‐myristate 13‐acetate (PMA)+anti‐CD3 monoclonal antibody or PMA + ionomycin. Different from T cell clones generated from peripheral blood, virtually all CD4+ T cell clones generated from human thymocytes produced high concentrations of IL‐2, IL‐4 and IL‐5, but no IFN‐γ, TNF‐β or IL‐10. Moreover, after activation, these clones expressed on their surface membrane both CD30 and CD40 ligand, but not the product of lymphocyte activation gene (LAG)‐3, and provided strong helper activity for IgE synthesis by allogeneic B cells. The Th2 cytokine pattern could not be modified by the addition of IFN‐γ. However, upon addition of exogenous IL‐12, the resulting CD4+ thymocyte clones produced TNF‐β, IFN‐γ, and IL‐10 in addition to IL‐4 and IL‐5. These results suggest that CD4+ human thymocytes have the potential to develop into cells producing the Th2 cytokines IL‐4 and IL‐5, whereas the ability to produce both Th1 cytokines and IL‐10 is acquired only after priming with IL‐12.