Cytokines Involved in the Pathophysiology of IgE Response

Abstract

Recent data in both mouse and human systems have clearly indicated that IL-4 plays an essential role in the induction of IgE response, whereas IFN-γ exerts an opposite effect on this phenomenon. However, IL-4 alone is unable to induce IgE synthesis. A prior membrane contact signal delivered by activated T cells is required by B cells to synthesize IgE in response to IL-4. A cognate interaction between B and T cells producing IL-4 (but not IFN-γ) is optimal for induction of IgE synthesis. However, when such IL-4 producing T cells are activated, they may provide B cells with a membrane signal, through a non-cognate interaction, which also results in induction of IgE synthesis. Other cytokines, such as IL-2 and IL-6, play an auxiliary role in IL-4 dependent IgE production.

Analyses at the clonal level of the profile of cytokine production by helper T cells have shown that imbalances between IL-4 and IFN-γ producing T cells can be detected in patients with hyperproduction of IgE. In children with hyper-IgE syndrome a strong reduction of circulating T cells able to produce IFN-γ (and TNF-α) was found, whereas both, reduction of IFN-γ-producing and increase of IL-4 producing T cells were found in patients with parasitic infestation. In allergic inflammatory infiltrates, such as those found in vernal conjuctivitis, helper T cells able to produce IL-4 and to induce IgE synthesis accounted for the large majority of infiltrating T cells. It is reasonable to suggest that systemic or microenvironmental alterations of the balance between IL-4- and IFN-γ-producing T cells may be involved, at least in part, in the pathophysiology of the increased igE response occurring in a number of human diseases.