The effect of interferon-γ, interleukin-4 and immunoglobulin receptor cross-linking of monocytes on allergen-specific T-cell response

Modulation of the proliferative responses of an allergen-specific human Th2 cell line by cytokine-treated monocytes was examined. The response of this cell line to the specific allergen, Amb a V (from short ragweed pollen), increased following the addition of interleukin-1β (IL-1β). However, in the presence of exogeneous interferon-γ (IFN-γ), there was greater than 40% reduction in the responsiveness of these T cells. The addition of IL-1β did not reverse the inhibitory effect of IFN-γ. To determine the primary target cell type for IFN-γ, autologous monocytes were pretreated with IL-4, IFN-γ, or medium alone, and used as antigen-presenting cells (APC). We showed that the responses of T cells to Amb a V were significantly down-regulated in the presence of autologous monocytes pretreated with IFN-γ, but not for monocytes pretreated with IL-4. Similar inhibitory effect of IFN-γ was confirmed using a human T-cell line specific for a ragweed allergen, Amb a I, and a human T-cell clone raised against ragweed extract. Cross-linking of CD23 (FcεRII) on monocytes pretreated with IFN-γ increased this inhibitory effect in an additive fashion, but, in the absence of IFN-γ treatment, such cross-linking had no effect. These inhibitory effects were not due to alterations in the surface expression of HLA-DR on the monocytess, and the addition of exogeneous IL-1β was unable to reverse these effects. In similar experiments, cross-linking of CD64 (FcγR) on monocytes showed no significant effects. In conclusion, IFN-γ is important in regulating the function of monocytes involved in Th2 cell responses to allergens. IL-4 treatment, as well as cross-linking of FcR of monocytes, have no direct effect on such response.