Regulation of Human Lymphocyte IL-4 Secretion by Intestinal Epithelial Cell-Derived Interleukin-7 and Transforming Growth Factor-β

A mucosal immune response to food antigens could result in detrimental hypersensitivity responses. Therefore, the response to many orally administered antigens is downregulated by mechanisms which are not completely understood. Intestinal epithelial cells (IEC) in these tissues may play a role in these regulatory mechanisms via their secreted cytokines. Experiments with human lymphocytes or isolated CD4⁺T cells cultured with 4-day culture supernatants from human colonic carcinoma cell lines revealed that the IEC cell lines normally secreted levels of IL-7 which could enhance IL-4, but not IL-2 or IFN-γ, secretion by stimulated mixtures of lymphocyes, but not purified CD4⁺T cells. However, acid treatment of the IEC culture supernatants to activate latent TGF-β resulted in a suppression IL-4, but not IL-2 or IFN-γ, secretion. These results indicate that under normal conditions, IEC secrete latent TGF-β and IL-7, the latter of which may enhance local IL-4 secretion. However, activation of the IEC-derived TGF-β may suppress local IL-4 secretion to suppress the induction of local Th2-type responses to intestinal lumenal antigens.