Expression of Cd28 and Cd86 by Human Eosinophils and Role in the Secretion of Type 1 Cytokines (Interleukin 2 and Interferon γ)

Abstract

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.

CD11c+ Eosinophils in the Murine Thymus: Developmental Regulation and Recruitment upon MHC Class I-Restricted Thymocyte Deletion

“…Moreover, eosinophils express a diverse array of cytokines and cell surface ligands (11,13), which suggest that it may have an immunomodulatory role. Eosinophils are associated with most inflammatory and infectious disorders and have been implicated beneficially in anti-tumor cytotoxicity and wound healing.…”

“…plexes in vitro induces IL-10 secretion in eosinophils taken from hypereosinophilic patients, while the ligation of CD28 induces IL-2 and IFN-␥ secretion (11).…”

“…Eosinophils can act as APC and express costimulatory molecules under activating conditions (11,14,15). Thymic eosinophils express class II molecules (Fig.…”

“…Conventionally associated with host defense against parasitic infection, through degranulation and release of toxic proteins, eosinophils also produce a variety of pro-and anti-inflammatory cytokines, growth factors, and chemokines (10 -13). Eosinophils can act as APC (14,15) and express several important costimulatory molecules (11,16), indicating that they could modulate adaptive immune responses. Eosinophils marginated in respiratory, gut, and urogenital subepithelium represent 95% of the total population, yet their physiological role is unclear.…”

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

“…Beside cytotoxic mediators, eosinophil granules contain multiple Th1, Th2, and immunoregulatory cytokines that are rapidly and selectively secreted (16). Among them, IFN, IFN-g, and TNF, which are known to play a major role during antitumor responses, are released by eosinophils (17,18). Some cellular interactions between eosinophils and tumor cells in situ have also been described (19,20).…”