2B4 (CD244) Is Expressed and Functional on Human Eosinophils

Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
The Journal of Immunology (Impact Factor: 4.92). 02/2005; 174(1):110-8. DOI: 10.4049/jimmunol.174.1.110
Source: PubMed


Eosinophils are present in parasitic, allergic, various immunological, and malignant disorders as well as in a variety of idiopathic hypereosinophilic syndromes. However, their exact role in some of these conditions remains elusive. They can be activated both in vivo and in vitro by various agonists, such as Igs, lipid mediators, and cytokines. By phenotyping the surface of the eosinophils, it may be possible to better define their function(s) in different pathophysiological settings. In the present work we screened eosinophils with a panel of Abs recognizing CD2 subfamily receptors usually present on a number of hemopoietic cells. We have demonstrated that human peripheral blood eosinophils, but not basophils or neutrophils, express NTB-A. In addition eosinophils express 2B4, CD84, CD58, and CD48, but not signaling lymphocytic activation molecule or CD2, on their surface (FACS). Cross-linking of 2B4 on eosinophils elicited a significant release of eosinophil peroxidase (30 min), IFN-gamma, and IL-4 (18 h). Moreover, activation of eosinophils via 2B4 induced eosinophil-mediated cytotoxicity toward two malignant cell lines, i.e., mouse mastocytoma P815 and EBV-infected 721.221 B cell lines. Cross-linking of 2B4 on the surface of eosinophils or pervenadate treatment elicited ERK and tyrosine phosphorylation, respectively. Furthermore, we showed that eosinophils express slam-associated protein. The demonstration that human eosinophils express a functional 2B4 receptor indicates a broader role for these cells in health and disease.

    • "). Eosinophils express various receptors for activating stimuli such as IL-2, C5a and PAF, interferon (IFN)-γ (Neves et al., 2008), IL-3, IL-5, GM-CSF, chemokine receptor 3 (CCR3), RANTES (Regulated on Activation, Normal T Expressed and Secreted) (Gregory et al., 2003) and the immunoglobulin A (Decot et al., 2005), which cause them to degranulate. Moreover they also express CD48, 2B4 (Munitz et al., 2005), pattern recognition receptors (PRRs) (Kvarnhammar and Cardell, 2012) and histamine receptors that signal via various mechanisms/pathways (summarized in (Davoine and Lacy, 2014). This would indicate their capacity to be involved in several kinds of pathologies. "
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    ABSTRACT: Mast cells are mostly known for their role in allergic diseases although in recent years it has become clear that they have a role in other diseases and in the body's defense against microbes. In most cases, but especially in allergy, eosinophils are present in the tissue within proximity of mast cells. Due to this spatio-temporal correlation we and others have postulated and described a crosstalk between these two cells, mediated via their released mediators and physical interactions, that is able to modulate each other's function and ultimately the outcome of the allergic inflammatory reaction. This review will focus on the functional unit between mast cells and eosinophils that we have named the "Allergic Effector Unit" and specifically highlight its role in allergy.
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    • "Costimulatory molecules including ICAM-1 and LFA-3 [39] have been shown to assist in antigen presentation by eosinophils lacking conventional costimulatory molecules [31]. There are two reports supporting LFA-3 expression by human basophils [40]-[41], but the results from our peptide assay suggest that this costimulatory molecule expression (if present) together with MHC Class II is not sufficient to induce T cell activation/proliferation to peptide. "
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    ABSTRACT: The antigen-presenting abilities of basophils and their role in initiating a Th2 phenotype is a topic of current controversy. We aimed to determine whether human basophils can be induced to express MHC Class II and act as antigen presenting cells for T cell stimulation. Isolated human basophils were exposed to a panel of cytokines and TLR-ligands and assessed for MHC Class II expression. MHC Class II was expressed in up to 17% of isolated basophils following incubation with a combination of IL-3, IFN-γ and GM-CSF for 72 hours. Costimulatory molecules (CD80 and CD86) were expressed at very low levels after stimulation. Gene expression analysis of MHC Class II-positive basophils confirmed up-regulation of HLA-DR, HLA-DM, CD74 and Cathepsin S. However, MHC Class II expressing basophils were incapable of inducing antigen-specific T cell activation or proliferation. This is the first report of significant cytokine-induced MHC Class II up-regulation, at both RNA and protein level, in isolated human basophils. By testing stimulation with relevant T cell epitope peptide as well as whole antigen, the failure of MHC Class II expressing basophils to induce T cell response was shown not to be solely due to inefficient antigen uptake and/or processing.
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    • "To understand how Fyn binding might promote 2B4 function, we analyzed tyrosine phosphorylation of Vav-1 and SHIP-1, the two most prominent tyrosine phosphorylation substrates triggered by 2B4 (Figures 2D and 2E; Chen et al., 2004; Mesecke et al., 2011; Munitz et al., 2005). Vav-1 is an exchange factor promoting multiple functions in immune cells, including "
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    ABSTRACT: The adaptor SAP, mutated in X-linked lymphoproliferative disease, has critical roles in multiple immune cell types. Among these, SAP is essential for the ability of natural killer (NK) cells to eliminate abnormal hematopoietic cells. Herein, we elucidated the molecular and cellular bases of this activity. SAP enhanced NK cell responsiveness by a dual molecular mechanism. It coupled SLAM family receptors to the kinase Fyn, which triggered the exchange factor Vav-1 and augmented NK cell activation. SAP also prevented the inhibitory function of SLAM family receptors. This effect was Fyn independent and correlated with uncoupling of SLAM family receptors from the lipid phosphatase SHIP-1. Both mechanisms cooperated to enable conjugate formation with target cells and to stimulate cytotoxicity and cytokine secretion by NK cells. These data showed that SAP secures NK cell activation by a dichotomous molecular mechanism, which is required for conjugate formation. These findings may have implications for the role of SAP in other immune cell types.
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