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Functional CD137 receptors are expressed by eosinophils from patients with IgE-mediated allergic responses but not by eosinophils from patients with non-IgE-mediated eosinophilic disorders.
J Allergy Clin Immunol. 2001 Jul; 108(1):21-8.JA

Abstract

BACKGROUND

CD137 (ILA/4-1BB), a member of the TNF/nerve growth factor receptor superfamily, has previously been suggested to be involved in T-cell activation and differentiation.

OBJECTIVE

The aim of this study was to investigate expression and potential function of CD137 in eosinophils.

METHODS

Eosinophils were isolated from normal control subjects as well as from patients with bronchial asthma, patients with atopic dermatitis, and patients with idiopathic eosinophilia. CD137 expression was analyzed by RT-PCR and flow cytometry. The in situ expression of CD137 on eosinophils in nasal polyp and skin tissues was analyzed through use of immunohistochemistry. To examine whether CD137 regulates eosinophil death and apoptosis, cells were stimulated with a plate-bound anti-CD137 antibody in the presence or absence of survival cytokines. Cell death was measured by means of an ethidium bromide exclusion test. Apoptosis was determined by analyzing phosphatidylserine surface exposure.

RESULTS

Blood and tissue eosinophils from patients with IgE-mediated allergic responses (atopic dermatitis, extrinsic asthma) express CD137. In contrast, eosinophils from normal control individuals and patients with non-IgE-mediated eosinophilic inflammatory responses (intrinsic asthma, idiopathic eosinophilia) express neither detectable levels of mRNA nor protein for CD137. Expression of CD137 in eosinophils was induced in vitro by stimulating the cells with supernatants derived from in vivo- or in vitro-activated T cells, suggesting that a soluble T cell-derived factor might be responsible for the observed phenomenon. Although CD137 expression was associated with increased IgE levels, IL-4 and IL-13 did not induce CD137 gene expression in eosinophils. Activation of CD137 abrogated both GM-CSF-mediated and IL-5-mediated antiapoptosis in CD137-expressing eosinophils but not in CD137-deficient eosinophils. In contrast, the survival effect of IFN-gamma was not affected by anti-CD137 treatment.

CONCLUSION

Our data indicate that CD137 activation might limit GM-CSF-mediated and IL-5-mediated antiapoptosis of eosinophils. The absence of this potential anti-inflammatory mechanism might further increase eosinophil numbers at inflammatory sites in patients with intrinsic asthma and patients with idiopathic eosinophilia. The T cell-derived factor that induces CD137 expression in eosinophils remains to be identified.

Authors+Show Affiliations

Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11447378

Citation

Heinisch, I V., et al. "Functional CD137 Receptors Are Expressed By Eosinophils From Patients With IgE-mediated Allergic Responses but Not By Eosinophils From Patients With non-IgE-mediated Eosinophilic Disorders." The Journal of Allergy and Clinical Immunology, vol. 108, no. 1, 2001, pp. 21-8.
Heinisch IV, Bizer C, Volgger W, et al. Functional CD137 receptors are expressed by eosinophils from patients with IgE-mediated allergic responses but not by eosinophils from patients with non-IgE-mediated eosinophilic disorders. J Allergy Clin Immunol. 2001;108(1):21-8.
Heinisch, I. V., Bizer, C., Volgger, W., & Simon, H. U. (2001). Functional CD137 receptors are expressed by eosinophils from patients with IgE-mediated allergic responses but not by eosinophils from patients with non-IgE-mediated eosinophilic disorders. The Journal of Allergy and Clinical Immunology, 108(1), 21-8.
Heinisch IV, et al. Functional CD137 Receptors Are Expressed By Eosinophils From Patients With IgE-mediated Allergic Responses but Not By Eosinophils From Patients With non-IgE-mediated Eosinophilic Disorders. J Allergy Clin Immunol. 2001;108(1):21-8. PubMed PMID: 11447378.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional CD137 receptors are expressed by eosinophils from patients with IgE-mediated allergic responses but not by eosinophils from patients with non-IgE-mediated eosinophilic disorders. AU - Heinisch,I V, AU - Bizer,C, AU - Volgger,W, AU - Simon,H U, PY - 2001/7/12/pubmed PY - 2001/8/24/medline PY - 2001/7/12/entrez SP - 21 EP - 8 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 108 IS - 1 N2 - BACKGROUND: CD137 (ILA/4-1BB), a member of the TNF/nerve growth factor receptor superfamily, has previously been suggested to be involved in T-cell activation and differentiation. OBJECTIVE: The aim of this study was to investigate expression and potential function of CD137 in eosinophils. METHODS: Eosinophils were isolated from normal control subjects as well as from patients with bronchial asthma, patients with atopic dermatitis, and patients with idiopathic eosinophilia. CD137 expression was analyzed by RT-PCR and flow cytometry. The in situ expression of CD137 on eosinophils in nasal polyp and skin tissues was analyzed through use of immunohistochemistry. To examine whether CD137 regulates eosinophil death and apoptosis, cells were stimulated with a plate-bound anti-CD137 antibody in the presence or absence of survival cytokines. Cell death was measured by means of an ethidium bromide exclusion test. Apoptosis was determined by analyzing phosphatidylserine surface exposure. RESULTS: Blood and tissue eosinophils from patients with IgE-mediated allergic responses (atopic dermatitis, extrinsic asthma) express CD137. In contrast, eosinophils from normal control individuals and patients with non-IgE-mediated eosinophilic inflammatory responses (intrinsic asthma, idiopathic eosinophilia) express neither detectable levels of mRNA nor protein for CD137. Expression of CD137 in eosinophils was induced in vitro by stimulating the cells with supernatants derived from in vivo- or in vitro-activated T cells, suggesting that a soluble T cell-derived factor might be responsible for the observed phenomenon. Although CD137 expression was associated with increased IgE levels, IL-4 and IL-13 did not induce CD137 gene expression in eosinophils. Activation of CD137 abrogated both GM-CSF-mediated and IL-5-mediated antiapoptosis in CD137-expressing eosinophils but not in CD137-deficient eosinophils. In contrast, the survival effect of IFN-gamma was not affected by anti-CD137 treatment. CONCLUSION: Our data indicate that CD137 activation might limit GM-CSF-mediated and IL-5-mediated antiapoptosis of eosinophils. The absence of this potential anti-inflammatory mechanism might further increase eosinophil numbers at inflammatory sites in patients with intrinsic asthma and patients with idiopathic eosinophilia. The T cell-derived factor that induces CD137 expression in eosinophils remains to be identified. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/11447378/Functional_CD137_receptors_are_expressed_by_eosinophils_from_patients_with_IgE_mediated_allergic_responses_but_not_by_eosinophils_from_patients_with_non_IgE_mediated_eosinophilic_disorders_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(01)89102-8 DB - PRIME DP - Unbound Medicine ER -