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Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+ TNF-α+ CD4+ T cells differentiation.
Clin Immunol 2015; 160(2):292-300CI

Abstract

Common variable immunodeficiency (CVID) refers to primary hypogammaglobulinemia with unknown pathogenesis. Although there is evidence for intrinsic B cell defects in some CVID patient groups, various abnormalities in cytokine production by T cells in CVID patients are frequently observed. Here, we demonstrate a relationship in the production of pro-inflammatory Th1 cytokines and regulatory B cells producing IL-10 between CVID patients and healthy controls. We describe CD19(+)CD24(hi)CD38(hi)IL-10(+) regulatory B cells generated after T cell stimulation of human peripheral blood lymphocytes ex vivo are able to suppress IFN-γ(+)TNF-α(+) producing CD4(+) T cells. This process is impaired in CVID patients, who present with both low numbers of CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells and increased numbers of IFN-γ(+)TNF-α(+)CD4(+) T cells. Disruption of the regulatory B cell response to T cell stimulation explains the excessive T cell activation regarded as an immunoregulatory abnormality that is a frequent finding in CVID patients.

Authors+Show Affiliations

Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic. Electronic address: marcela.vlkova@fnusa.cz.Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Medical Faculty, Charles University Prague, University Hospital Motol, Prague, Czech Republic.Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.Centre for Rheumatology Research, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.Centre for Rheumatology Research, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.

Pub Type(s)

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

Language

eng

PubMed ID

26232673

Citation

Vlkova, Marcela, et al. "Regulatory B Cells in CVID Patients Fail to Suppress Multifunctional IFN-γ+ TNF-α+ CD4+ T Cells Differentiation." Clinical Immunology (Orlando, Fla.), vol. 160, no. 2, 2015, pp. 292-300.
Vlkova M, Ticha O, Nechvatalova J, et al. Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+ TNF-α+ CD4+ T cells differentiation. Clin Immunol. 2015;160(2):292-300.
Vlkova, M., Ticha, O., Nechvatalova, J., Kalina, T., Litzman, J., Mauri, C., & Blair, P. A. (2015). Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+ TNF-α+ CD4+ T cells differentiation. Clinical Immunology (Orlando, Fla.), 160(2), pp. 292-300. doi:10.1016/j.clim.2015.06.013.
Vlkova M, et al. Regulatory B Cells in CVID Patients Fail to Suppress Multifunctional IFN-γ+ TNF-α+ CD4+ T Cells Differentiation. Clin Immunol. 2015;160(2):292-300. PubMed PMID: 26232673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+ TNF-α+ CD4+ T cells differentiation. AU - Vlkova,Marcela, AU - Ticha,Olga, AU - Nechvatalova,Jana, AU - Kalina,Tomas, AU - Litzman,Jiri, AU - Mauri,Claudia, AU - Blair,Paul A, Y1 - 2015/07/29/ PY - 2015/03/04/received PY - 2015/06/26/revised PY - 2015/06/28/accepted PY - 2015/8/2/entrez PY - 2015/8/2/pubmed PY - 2015/12/17/medline KW - B cell KW - Common variable immunodeficiency (CVID) KW - Cytokine production KW - Flow cytometry KW - T cell SP - 292 EP - 300 JF - Clinical immunology (Orlando, Fla.) JO - Clin. Immunol. VL - 160 IS - 2 N2 - Common variable immunodeficiency (CVID) refers to primary hypogammaglobulinemia with unknown pathogenesis. Although there is evidence for intrinsic B cell defects in some CVID patient groups, various abnormalities in cytokine production by T cells in CVID patients are frequently observed. Here, we demonstrate a relationship in the production of pro-inflammatory Th1 cytokines and regulatory B cells producing IL-10 between CVID patients and healthy controls. We describe CD19(+)CD24(hi)CD38(hi)IL-10(+) regulatory B cells generated after T cell stimulation of human peripheral blood lymphocytes ex vivo are able to suppress IFN-γ(+)TNF-α(+) producing CD4(+) T cells. This process is impaired in CVID patients, who present with both low numbers of CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells and increased numbers of IFN-γ(+)TNF-α(+)CD4(+) T cells. Disruption of the regulatory B cell response to T cell stimulation explains the excessive T cell activation regarded as an immunoregulatory abnormality that is a frequent finding in CVID patients. SN - 1521-7035 UR - https://www.unboundmedicine.com/medline/citation/26232673/Regulatory_B_cells_in_CVID_patients_fail_to_suppress_multifunctional_IFN_γ+_TNF_α+_CD4+_T_cells_differentiation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1521-6616(15)30004-8 DB - PRIME DP - Unbound Medicine ER -