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

Munitz, Ariel; Bachelet, Ido; Fraenkel, Shira; Katz, Gil; Mandelboim, Ofer; Simon, Hans‐Uwe; Moretta, Lorenzo; Colonna, Marco; Levi‐Schaffer, Francesca

doi:10.4049/jimmunol.174.1.110

Cited by 103 publications

(82 citation statements)

References 55 publications

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“…Indeed, we recently demonstrated that human eosinophils express gd TCR and showed its involvement in Colo-205 cell death induction (18). Another receptor shared between T cells and eosinophils, 2B4, a member of the CD2 family, has also been involved in the cytotoxic activity of eosinophils toward a B lymphoma cell line (21). However, in our study concerning a different target cell, the colorectal carcinoma cell line, 2B4 only played a minor role in tumoricidal activity (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Eosinophil granule proteins that are released upon activation are known to be highly cytotoxic at least in vitro (15), but receptors triggering eosinophil degranulation and mediator release upon contact with tumor cells are unknown. So far, a single study demonstrated the cytotoxic activity of eosinophils toward a B lymphoma cell line in vitro and the implication of 2B4 receptor, a member of the CD2 family, in antitumor responses of eosinophils (21). In a recent study, we showed that eosinophils express the CD3-gdTCR, a receptor shared with the gd T cells (18).…”

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confidence: 99%

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

Legrand

Driss

Delbeke

et al. 2010

The Journal of Immunology

144

135

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Peripheral blood and tissue eosinophilia is a prominent feature in allergic diseases and helminth infections. In cancer patients, tumor-associated tissue eosinophilia is frequently observed. Tumor-associated tissue eosinophilia can be associated with a favorable prognosis, notably in colorectal carcinoma. However, underlying mechanisms of eosinophil contribution to antitumor responses are poorly understood. We have in this study investigated the direct interactions of human eosinophils with Colo-205, a colorectal carcinoma cell line, and show that eosinophils induce apoptosis and directly kill tumor cells. Using blocking Abs, we found that CD11a/CD18 complex is involved in the tumoricidal activity. Coculture of eosinophils with Colo-205 led to the release of eosinophil cationic protein and eosinophil-derived neurotoxin as well as TNF-α secretion. Moreover, eosinophils expressed granzyme A, which was released upon interaction with Colo-205, whereas cytotoxicity was partially inhibited by FUT-175, an inhibitor of trypsin-like enzymatic activity. Our data present the first demonstration, to our knowledge, that granzyme A is a cytotoxic mediator of the eosinophil protein arsenal, exerting eosinophil tumoricidal activity toward Colo-205, and provide mechanistic evidence for innate responses of eosinophil against tumor cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Legrand

Driss

Delbeke

et al. 2010

The Journal of Immunology

144

135

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“…2B4 is expressed by all NK cells, as well as a subset of memory CD8 1 abT cells, gdT cells, basophils, monocytes and eosinophils [11][12][13][14][15]. 2B4 binds to the glycophosphoinositol anchored protein, CD48, expressed on all hematopoietic cells, with a similar affinity in mouse and human [16,17].…”

Section: Introductionmentioning

confidence: 99%

Functional role of human NK cell receptor 2B4 (CD244) isoforms

et al. 2009

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TX, USA2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM/CD150), is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Human NK cells express two isoforms of 2B4, h2B4-A and h2B4-B that differ in a small portion of the extracellular domain. In the present investigation, we have studied the functions of h2B4-A and h2B4-B. Our study demonstrated that these two isoforms differ in their binding affinity for CD48, which results in differential cytotoxic activity as well as intracellular calcium release by NK cells upon target cell recognition. Analysis of the predicted 3-D structure of the two isoforms showed conformational differences that could account for their differences in binding affinity to CD48. h2B4-A was able to mediate natural cytotoxicity against CD48-expressing K562 target cells and induce intracellular calcium release, whereas h2B4-B showed no effects. NK-92MI, U937, THP-1, KU812, primary monocytes, basophils and NK cells showed expression of both h2B4-A and h2B4-B whereas YT and IL-2-activated NK cells did not show any h2B4-B expression. Stimulation of NK cells through 2B4 resulted in decreased mRNA levels of both h2B4-A and h2B4-B indicating that down-regulation of 2B4 isoforms may be an important factor in controlling NK cell activation during immune responses.Key words: Cell activation . Cell surface molecules . NK cells Introduction NK cells are a fundamental component of the innate immune system, capable of recognizing and destroying tumor cells as well as cells that have been infected by viruses or bacteria [1]. In addition to their role in innate immune responses, interactions between NK cells and dendritic cells regulate the adaptive immune response to pathogens [2]. NK cell functions are regulated by a dynamic interplay between activating and inhibitory signals transmitted by distinct classes of receptors found on their surface [3,4]. The balance between positivesignaling receptors and negative-signaling receptors ultimately determines the outcome of NK cell-target cell encounters [5,6].2B4 (CD244), belongs to the signaling lymphocyte-activation molecule (SLAM) family of receptors, which includes SLAM (CD150), CD84, NTB-A (Ly-108), lymphocyte antigen 9 (Ly9; CD229), and CD2-subset 1 (CS1) (also termed CRACC or CD319) [7][8][9][10]. 2B4 is expressed by all NK cells, as well as a subset of memory CD8 1 abT cells, gdT cells, basophils, monocytes and eosinophils [11][12][13][14][15]. 2B4 binds to the glycophosphoinositol anchored protein, CD48, expressed on all hematopoietic cells, with a similar affinity in mouse and human [16,17]. Engagement of 2B4 via interaction with specific antibodies or CD48 induces cytokine secretion (IFN-g) and enhances non-MHC-restricted 1632killing by NK cells [12,16,18]. 2B4 can also function as a ligand on target cells and stimulate NK cells through the engagement of CD48 [19]. 2B4 was initially identified as an activating receptor in non-MHC-restricted killing of NK and T cells [12,20]. Some studies with human ...

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“…Eosinophils were purified from peripheral blood of atopic asthmatics (see below) or age-and sex-matched normal individuals (blood eosinophil levels 5-10%) by MACS-negative immunomagnetic separation as described previously (10). Asthmatic donors were all atopic individuals (total IgE Ͼ100 IU/ml blood) requiring intermittent ␤ 2 -agonist treatment (forced expiratory volume 1 values ranging from 75-90% of normal).…”

Section: Human Peripheral Blood Eosinophil Donorsmentioning

confidence: 99%

“…These include CD2, CD48 (Blast-1 and BCM-1), CD58 (LFA-3), CD84 (Ly9B), CD150 (signaling lymphocytic activation molecule), CD229 (Ly9), 2B4 (CD244), BCM-like membrane protein, SF2001 (CD2F-10), NTB-A (SF2000 and Ly108), and CS1 (CD1-like receptor-activating cytotoxic effects) (9). We demonstrated that 2B4, the high-affinity ligand for CD48, activates human eosinophils to release IL-4 and IFN-␥, and to develop cytotoxic activity against tumor cell lines in vitro (10). Inasmuch as eosinophils express both CD48 and 2B4, we have focused our current study on CD48.…”

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confidence: 99%

CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils

Munitz

Bachelet

Eliashar

et al. 2006

The Journal of Immunology

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Eosinophils are involved in a variety of allergic, parasitic, malignant, and idiopathic disorders by releasing a variety of factors including specific granule proteins, lipid mediators, and proinflammatory and immunoregulatory cytokines and chemokines. In addition, they interact with various cell types in the inflamed tissue. Yet, the mechanism of eosinophil activation is still poorly understood. Recently, we described the expression and function of the CD2-subfamily of receptors and especially 2B4 on human eosinophils. In this study we focus on CD48, the high-affinity ligand of 2B4. CD48 is a GPI-anchored protein involved in cellular activation, costimulation, and adhesion, but has not been studied on eosinophils. We demonstrate that human eosinophils from atopic asthmatics display enhanced levels of CD48 expression and that IL-3 up-regulates CD48 expression. Furthermore, cross-linking CD48 on human eosinophils triggers release of eosinophil granule proteins. Assessment of CD48 expression in a murine model of experimental asthma revealed that CD48 is induced by allergen challenge and partially regulated by IL-3. Additionally, anti-IL-3 reduces CD48 expression and the degree of airway inflammation. Thus, CD48 is an IL-3-induced activating receptor on eosinophils, likely involved in promoting allergic inflammation.

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

Cited by 103 publications

References 55 publications

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

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

Functional role of human NK cell receptor 2B4 (CD244) isoforms

CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils

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