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The TH1 phenotype of follicular helper T cells indicates an IFN-γ–associated immune dysregulation in patients with CD21low common variable immunodeficiency 

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Presentation on theme: "The TH1 phenotype of follicular helper T cells indicates an IFN-γ–associated immune dysregulation in patients with CD21low common variable immunodeficiency "— Presentation transcript:

1 The TH1 phenotype of follicular helper T cells indicates an IFN-γ–associated immune dysregulation in patients with CD21low common variable immunodeficiency  Susanne Unger, MSc, Maximilian Seidl, MD, Pauline van Schouwenburg, PhD, Mirzokhid Rakhmanov, PhD, Alla Bulashevska, PhD, Natalie Frede, MD, Bodo Grimbacher, MD, Jens Pfeiffer, MD, Klaudia Schrenk, Luis Munoz, MD, PhD, Leif Hanitsch, MD, Ina Stumpf, Fabian Kaiser, MD, Oliver Hausmann, MD, Florian Kollert, MD, Sigune Goldacker, MD, Mirjam van der Burg, PhD, Baerbel Keller, PhD, Klaus Warnatz, MD  Journal of Allergy and Clinical Immunology  Volume 141, Issue 2, Pages (February 2018) DOI: /j.jaci Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 The CD4 T-cell compartment is skewed toward TH1 in patients with CVIDc. A-D, cTFH1, cTFH1/17, cTFH2, and cTFH17 (Fig 1, A and C) and TH1, TH1/17, TH2, and TH17 (Fig 1, B and D) cell subsets in PBMCs of HDs and patients with CVID. E, Expression of TBX21 in CD4 memory T cells. F, TH1, TH1/17, TH2, and TH17 subsets in tonsils from HDs and SLOs from patients with CVID. *P < .05, **P < .01, ***P < .005, and ****P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Increased IFN-γ production by memCD4 T cells in patients with CVID. A, Intracellular IFN-γ production on stimulation with plate-bound anti-CD3 and soluble anti-CD28 or phorbol 12-myristate 13-acetate (PMA) and ionomycin (Iono) in peripheral blood memCD4 T cells. B, Intracellular IFN-γ production on stimulation with PMA plus ionomycin in TFH cells of tonsils from patients with HD and SLOs from patients with CVID. C, IFN-γ concentration in serum. *P < .05, **P < .01, and ****P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Effect of IFN-γ on GC-derived B cell populations. A, Correlation of IFN-γ production on stimulation with phorbol 12-myristate 13-acetate (PMA) plus ionomycin in TFH cells with class-switched (cs) memory B cells in SLOs. B, IgG, IgA, and IgM production of allogenic T-cell/B-cell cocultures of tonsils in the presence of IFN-γ, IFN-γ blockade (aIFN-γ), or isotype control (iso) after 5 days. C, Distribution of IgG subclass transcripts in SLOs. *P < .05 and **P < .01. ns, Not significant. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Increased T-bet expression in lymph nodes from patients with CVID and CD21low B cells. A, Lymph node sections from control subjects and patients with CCID were stained for CD20 (red) and T-bet (brown). Lymph nodes from patients with CVID contained increased numbers of T-bet+ nuclei in GCs, especially in irregularly shaped GCs. High-resolution versions of the slides for use with the Virtual Microscope are available as eSlide: VM04082, eSlide: VM04083, eSlide: VM04084 and eSlide: VM B, Accumulation of T-bet+ cells in irregularly shaped GCs. C, Accumulation of monocytoid T-bet+ B cells in lymph nodes from patients with CVID. High-resolution versions of the slides for use with the Virtual Microscope are available as eSlide: VM04086, eSlide: VM04087, eSlide: VM04088 and eSlide: VM D, FcRL4 and CD21 expression on B cells in tonsils from patients with HDs and a patient with CVID. E, FcRL4+CD21low monocytoid B cells in SLOs from patients with CVID express higher T-bet levels compared with tonsils from HDs. *P < .05. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Interferon signature in CD21low B cells. A, Correlation of monocytoid T-bet+ B cells in SLOs with CD21low B cells in blood. B, Increased FcRL4 expression in CD21low B cells. C, Increased T-bet expression in CD21low B cells in blood. D, Interferon-responsive genes in CD21low B cells (4 patients with CVID) and naive B cells (3 patients with CVID and 4 HDs). Columns represent individual samples. Color changes indicate expression levels relative to the average of the sample population according to the color bar. Validation is indicated by an arrowhead. **P < .01 and ****P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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