The effect of interferon-gamma, 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-1 beta (IL-1 beta). However, in the presence of exogenous interferon-gamma (IFN-gamma), there was greater than 40% reduction in the responsiveness of these T cells. The addition of IL-1 beta did not reverse the inhibitory effect of IFN-gamma. To determine the primary target cell type for IFN-gamma, autologous monocytes were pretreated with IL-4, IFN-gamma, 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-gamma, but not for monocytes pretreated with IL-4. Similar inhibitory effect of IFN-gamma 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 (Fc epsilon RII) on monocytes pretreated with IFN-gamma increased this inhibitory effect in an additive fashion, but, in the absence of IFN-gamma treatment, such cross-linking had no effect. These inhibitory effects were not due to alterations in the surface expression of HLA-DR on the monocytes, and the addition of exogenous IL-1 beta was unable to reverse these effects. In similar experiments, cross-linking of CD64 (Fc gamma R) on monocytes showed no significant effects. In conclusion, IFN-gamma 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.
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224-6801.
M
M
Kumai
G
G
Krishnaswamy
D G
DG
Marsh
S K
SK
Huang
D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D010940:Plant Proteins; D011961:Receptors, Fc / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D010940:Plant Proteins; D011961:Receptors, Fc; C069543:group 5 allergens, Ambrosia; D015847:Interleukin-4; D007371:Interferon-gamma