Human Th1 cells preferentially induce interleukin (IL)‐1β while Th2 cells induce IL‐1 receptor antagonist production upon cell/cell contact with monocytes

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Abstract
The role of human T cells in the induction and regulation, upon cell/cell contact, of inflammatory responses by monocytic cells was investigated. The production of interleukin (IL)‐1β and IL‐1 receptor antagonist (IL‐1Ra) by the monocytic THP‐1 cell line was measured upon contact with either Th1 or Th2 cell clones. CD4+ T cell clones specific for purified protein derivative of Mycobacterium tuberculosis, predominantly Th1 [high interferon (IFN)‐γ and low IL‐4 producers], or tetanus toxoid, predominantly Th2 (low IFN‐γ and high IL‐4 producers), were generated. Cell membranes from antigen‐stimulated, but not from resting T cell clones induced dose‐dependent cytokine production by THP‐1 cells. Th1 clones induced higher levels of IL‐1β production (484–806 pg/ml) than did Th2 clones (21–114 pg/ml). In contrast, Th1 clones induced lower levels of IL‐1Ra (0.9–7.8 ng/ml) than did Th2 clones (7.0–49.6 ng/ml). Similar results were obtained when T cell clones were activated by cross‐linked CD3 and CD28. IL‐1β production by THP‐1 cells correlated with IFN‐γ production by T cell clones but was unaffected by IFN‐γ neutralization. IL‐1Ra production by THP‐1 cells correlated with IL‐4 production by T cells and was partially inhibited by IL‐4 neutralization. These data indicate that activated Th1 and Th2 cells express different molecules on the cell surface able to induce distinct pro‐inflammatory (IL‐1β) or anti‐inflammatory (IL‐1Ra) responses in monocytes. This differential induction of molecules with opposite effects on inflammation stresses the functional heterogeneity in CD4+ T cells.