Eosinophils are the source of various immunoregulatory cytokines, but the membrane molecules involved in their secretion have not been clearly identified. Here we show that peripheral blood eosinophils from hypereosinophilic patients could express membrane CD86 but not CD80. The T cell costimulatory molecule CD28 is also detected on the eosinophil surface. CD28 ligation but not CD86 ligation resulted in interleukin (IL)-2 and interferon (IFN)-γ secretion by eosinophils, whereas IL-4, IL-5, and IL-10 were not detected. In contrast to T cells requiring two signals for effective stimulation, CD28 ligation alone was sufficient for optimal eosinophil activation. Eosinophil-derived IL-2 and IFN-γ were biologically active, as supernatants from anti-CD28–treated cells were able to induce CTLL-2 proliferation and major histocompatibility complex class II expression on the colon carcinoma cell line Colo 205, respectively. Addition of secretory immunoglobulin (Ig)A–anti-IgA complexes, which could induce the release of IL-10, very significantly inhibited both CD28-mediated IL-2 and IFN-γ release. These results suggest that the release of type 1 (IFN-γ and IL-2) versus type 2 cytokines by eosinophils is not only differential but also dependent on cross-regulatory signals. They confirm that through activation of costimulatory molecules, eosinophils could function as an immunoregulatory cell involved in the release of both type 1 and type 2 cytokines.
Besides cytotoxic mediators, human eosinophils can produce proinflammatory and anti–inflammatory cytokines, as well as growth factors and chemokines. The demonstration that eosinophils from patients could produce IL–5, IL–4 and IL–2 suggested their participation in the regulation of immune response. In the present work, we have examined the presence of Th1 (IFN–γ, IL–2) and Th2 (IL–4, IL–5, IL–10 and IL–13) cytokines in eosinophils from patients or donors by intracellular flow cytometry, and by immunocytochemistry. Whereas almost 100% eosinophils expressed intracellular IFN–γ, IL–2 and IL–10, the expression of IL–4, IL–5 and IL–13 is more variable and increased in patients versus donors. The differential release by eosinophils of Th2 versus Th1 cytokines is suggested both by the decrease of the intracellular content after culture, restricted to IL–4, IL–5 and IL–13, associated with an accumulation of IL–4 and IL–5 in the presence of Brefeldin. These results indicate that, through the preferential release of Th2 cytokines, human eosinophils can participate in the polarization of the immune response.
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