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CD4+CD25+Foxp3+ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency.
Int J Immunopathol Pharmacol. 2016 Jun; 29(2):241-51.IJ

Abstract

Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies characterized by decreased serum immunoglobulin G along with a decrease in serum IgA and/or IgM, defective specific antibody production, and recurrent bacterial infections. Abnormal lymphocyte trafficking, dysregulated cellular responses to chemokines, and uncontrolled T cell polarization may be involved in the pathogenesis and may help to understand the clinical complications. We evaluated T helper cell subsets (chemokine receptors CCR4, CCR5, and CCR7), expressions on T lymphocytes, intracellular cytokines - IL-2, IL-4, IL-13, IFN- γ-on CD4(+) T cells, and expression of CD4(+)CD25(+)Foxp3(+) regulatory T cells of 20 CVID patients and 26 healthy controls. Autoimmune clinical findings and other complications were also determined. Percentages and absolute numbers of CD4(+)CD25(+) Foxp3(+) cells did not show any significant difference between CVID cases and healthy controls nor between severe and moderate disease patients. The only significant difference regarding Th1 and Th2 type intracellular cytokines was the decreased absolute numbers of CD3(+)CD4(+)IL4(+) cells in CVID cases. There were some findings about T helper cell type dominance in CVID patients such as positive correlation between hepatomegaly and high IL-2 and IFN-γ in CD3(+)CD4(+) cells and very high expression of CCR5 (Th1) on CD3(+)CD4(+) cells in patients with granuloma. Th1 (CCR5) and Th2 (CCR4) type chemokine receptors did not show any dominance in CVID cases. However, frequencies of CCR7 expressing CD3(+) T cells, CD3(+)CD4(+) T helper cells and CD3(+)CD8(+) T cytotoxic cells were significantly lower in severe CVID patients. In addition, presence of autoimmune clinical findings was negatively correlated with CCR7(+) cells. As CCR7 is a key mediator balancing immunity and tolerance in the immune system, the abnormality of this mediator may contribute to the profound immune dysregulation seen in CVID. In addition, Th1 cells seem to be more involved in the disease pathogenesis than Th2 cells.

Authors+Show Affiliations

Ege University, Faculty of Medicine, Department of Pediatric Immunology, Izmir, Turkey.Ege University, Faculty of Medicine, Department of Pediatric Immunology, Izmir, Turkey elif.azarsiz@ege.edu.tr.Ege University, Faculty of Medicine, Department of Pediatric Immunology, Izmir, Turkey.Ege University, Faculty of Medicine, Department of Pediatric Immunology, Izmir, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26684629

Citation

Kutukculer, Necil, et al. "CD4+CD25+Foxp3+ T Regulatory Cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) Type Chemokine Receptors and Intracellular Cytokines in Children With Common Variable Immunodeficiency." International Journal of Immunopathology and Pharmacology, vol. 29, no. 2, 2016, pp. 241-51.
Kutukculer N, Azarsiz E, Aksu G, et al. CD4+CD25+Foxp3+ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency. Int J Immunopathol Pharmacol. 2016;29(2):241-51.
Kutukculer, N., Azarsiz, E., Aksu, G., & Karaca, N. E. (2016). CD4+CD25+Foxp3+ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency. International Journal of Immunopathology and Pharmacology, 29(2), 241-51. https://doi.org/10.1177/0394632015617064
Kutukculer N, et al. CD4+CD25+Foxp3+ T Regulatory Cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) Type Chemokine Receptors and Intracellular Cytokines in Children With Common Variable Immunodeficiency. Int J Immunopathol Pharmacol. 2016;29(2):241-51. PubMed PMID: 26684629.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD4+CD25+Foxp3+ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency. AU - Kutukculer,Necil, AU - Azarsiz,Elif, AU - Aksu,Guzide, AU - Karaca,Neslihan Edeer, Y1 - 2015/12/18/ PY - 2015/01/06/received PY - 2015/10/02/accepted PY - 2015/12/20/entrez PY - 2015/12/20/pubmed PY - 2017/4/4/medline KW - CVID KW - Th1/Th2 chemokine receptors KW - Treg cells KW - intracellular cytokines SP - 241 EP - 51 JF - International journal of immunopathology and pharmacology JO - Int J Immunopathol Pharmacol VL - 29 IS - 2 N2 - Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies characterized by decreased serum immunoglobulin G along with a decrease in serum IgA and/or IgM, defective specific antibody production, and recurrent bacterial infections. Abnormal lymphocyte trafficking, dysregulated cellular responses to chemokines, and uncontrolled T cell polarization may be involved in the pathogenesis and may help to understand the clinical complications. We evaluated T helper cell subsets (chemokine receptors CCR4, CCR5, and CCR7), expressions on T lymphocytes, intracellular cytokines - IL-2, IL-4, IL-13, IFN- γ-on CD4(+) T cells, and expression of CD4(+)CD25(+)Foxp3(+) regulatory T cells of 20 CVID patients and 26 healthy controls. Autoimmune clinical findings and other complications were also determined. Percentages and absolute numbers of CD4(+)CD25(+) Foxp3(+) cells did not show any significant difference between CVID cases and healthy controls nor between severe and moderate disease patients. The only significant difference regarding Th1 and Th2 type intracellular cytokines was the decreased absolute numbers of CD3(+)CD4(+)IL4(+) cells in CVID cases. There were some findings about T helper cell type dominance in CVID patients such as positive correlation between hepatomegaly and high IL-2 and IFN-γ in CD3(+)CD4(+) cells and very high expression of CCR5 (Th1) on CD3(+)CD4(+) cells in patients with granuloma. Th1 (CCR5) and Th2 (CCR4) type chemokine receptors did not show any dominance in CVID cases. However, frequencies of CCR7 expressing CD3(+) T cells, CD3(+)CD4(+) T helper cells and CD3(+)CD8(+) T cytotoxic cells were significantly lower in severe CVID patients. In addition, presence of autoimmune clinical findings was negatively correlated with CCR7(+) cells. As CCR7 is a key mediator balancing immunity and tolerance in the immune system, the abnormality of this mediator may contribute to the profound immune dysregulation seen in CVID. In addition, Th1 cells seem to be more involved in the disease pathogenesis than Th2 cells. SN - 2058-7384 UR - https://www.unboundmedicine.com/medline/citation/26684629/CD4+CD25+Foxp3+_T_regulatory_cells_Th1__CCR5_IL_2_IFN_γ__and_Th2__CCR4_IL_4_Il_13__type_chemokine_receptors_and_intracellular_cytokines_in_children_with_common_variable_immunodeficiency_ L2 - http://journals.sagepub.com/doi/full/10.1177/0394632015617064?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -