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Regulation of T helper cell cytokine expression: functional dichotomy of antigen‐presenting cells

A bias to either cell‐mediated or antibody‐mediated effector mechanisms is induced in an immune response against a pathogen, if activated T helper cells (Th) predominantly express Th1 [interleukin (IL)‐2, interferon (IFN)‐γ, and tumor necrosis factor (TNF)‐β] or Th2 (IL‐4, IL‐5, IL‐6 and IL‐10) cytokines. Here we provide evidence that, due to the capability to secrete IL‐1, macrophages, but not B cells, as antigen‐presenting cells (APC) induce production of IFN‐γ in resting Th cells. Normal murine splenic Th cells were activated in vitro with the superantigen Staphylococcus aureus enterotoxin B (SEB) presented by macrophages as compared to other APC from murine spleen. As determined by immunofluorescence, Th cells producing IL‐2 but almost none producing IL‐4 and IL‐5 are generated, irrespective of the type of APC. Generation of IFN‐γ‐producing Th cells is largely dependent on presentation of SEB by macrophages. The requirement for macrophages, however, is overcome if IL‐1 is provided. Expression of IFN‐y by Th cells is not induced, if production of IL‐1 by macrophages is inhibited by IL‐10. Our results suggest a functional dichotomy of APC: normal resting Th cells differentiate into IL‐2 and IFN‐γ secreting cells (Th1 cells) if antigen is presented by macrophages, whereas presentation by B cells generates Th cells secreting IL‐2, which might differentiate into Th2 cells upon re‐stimulation.