Interleukin 4 production by CD4+ T cells from allergic individuals is modulated by antigen concentration and antigen-presenting cell type.

作者：Heather Secrist, Rosemarie H. DeKruyff, Dale T. Umetsu · 发表于：The Journal of Experimental Medicine · 年份：1995 · DOI：10.1084/jem.181.3.1081 · 被引用次数：265 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

We have previously shown that CD4+ T cells from allergic individuals are predisposed to produce interleukin (IL)-4 in response to allergens, and that allergen immunotherapy greatly reduced IL-4 production in an allergen-specific fashion. The mechanism that results in the reduction of IL-4 synthesis in treated individuals is unknown, but because clinical improvement during immunotherapy is associated with the administration of the highest doses of allergen, we hypothesized that high concentration of allergen results in the downregulation of IL-4 synthesis in CD4+ T cells. In this report, we demonstrated that CD4+ T cells from allergic donors produced high levels of IL-4 when stimulated with low concentrations of allergen (0.003-0.01 micrograms/ml), particularly when B cell-enriched populations presented the antigen. In contrast, the same responding CD4+ T cell population produced little IL-4 when stimulated with high concentrations of allergen (10-30 micrograms/ml), especially when monocytes were used as antigen-presenting cells (APC). The quantity of IL-4 produced was also found to be inversely related to the extent of proliferation of the CD4+ T cells in response to allergen/antigen; maximal proliferation of CD4+ T cells occurred in response to high concentrations of antigen when IL-4 production was minimal. Antigen presentation by B cell-enriched populations, instead of monocytes, induced less CD4+ T cell proliferation, but induced much greater IL-4 synthesis. Moreover, the...