Interferon α increases the frequency of interferon γ-producing human CD4+ T cells

Abstract

An increased ratio of T helper type 2 (Th2)- vs Th1-like cells contributes to the immune dysregulation in allergic disease situations and in many chronic infections, including AIDS. Th2-type immune responses are characterized by Th cells that produce increased levels of interleukin-4 (IL-4) and decreased levels of interferon γ (IFN-γ). The induction of either a Th1- or a Th2-like phenotype may be critically controlled by the antigen-presenting cells and their cytokines, e.g., IFN-α. In this study we have determined the frequencies of potential IL-4- and/or IFN-γ-producing T cells in the peripheral blood of randomly selected healthy individuals, and analyzed whether IFN-α controls IL-4 and/or IFN-γ production. Purified CD4+ or CD8+ T cells were stimulated for 24 h via the T cell receptor/CD3 complex in the presence or absence of IFN-α, and single IL-4- and IFN-γ-secreting cells were detected in enzyme-linked immunospot assays. In the absence of IFN-α, CD4 cells produced IFN-γ at frequencies of 1:50-300, and produced IL-4 at frequencies of 1:110-<1:100,000. Addition of IFN-α during the activation of CD4 cells increased the levels of IFN-γ mRNA. As a consequence, the numbers of IFN-γ-producing CD4 cells and the amounts of secreted IFN-γ increased 10-fold. In contrast, IFN-α did not increase the frequency of 1L-4-secreting CD4 cells. In the absence of IFN-α, addition of exogenous IL-4 to cultures ot IL-4 cells suppressed IFN-γ secretion by 70%. However, in the presence of IFN-α, IL-4 did not display any suppressive effect. Compared with CD4 cells, CD8 cells produced IFN-γ more frequently (1:5-10) but IL-4 less frequently (1:5,300 to <1:100,000). IFN-α did not display any effect on the frequency of either IFN-γ or IL-4 production by CD8 cells. Taken together the results indicate that IFN-α increases the frequency of IFN-γ-secreting CD4 Th cells and antagonizes the suppressive effect of IL-4 on IFN-γ production. As a consequence, IFN-α may favor the induction and maintenance of Th1-like cells and thereby counteract Th2-driven allergic immune responses.