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Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency  Sayed Mahdi Marashi, PhD, Mohammed.

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Presentation on theme: "Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency  Sayed Mahdi Marashi, PhD, Mohammed."— Presentation transcript:

1 Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency  Sayed Mahdi Marashi, PhD, Mohammed Raeiszadeh, MPhil, Victoria Enright, MSc, Fariba Tahami, MSc, Sarita Workman, MSc, Ronnie Chee, MBBS, A. David Webster, MD, Richard S.B. Milne, PhD, Vincent C. Emery, PhD  Journal of Allergy and Clinical Immunology  Volume 129, Issue 5, Pages e3 (May 2012) DOI: /j.jaci Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Analysis of CD4+/CD8+ T-cell ratio. The frequency of CD4+ (A) and CD8+ (B) T cells as a percentage of total lymphocytes and the CD4+/CD8+ ratio (C) are shown for patients with CVID (with and without CMV infection) and healthy control subjects. Bars indicate the mean percentage values. P values are for the indicated pairwise comparisons. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Analysis of selected CD4+ and CD8+ T-cell subsets. Whole blood was analyzed for CD4+ memory cells (A), T follicular helper cells (B), late effector CD8+ T cells (C), and effector CD8+ T cells (D). Bars indicate mean values. P values are for the indicated pairwise comparisons. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Lymphocyte phenotypes in patients with CVID. A and B, Lymphocyte phenotypes in patients with inflammatory (black bars) or noninflammatory (white bars) CVID (means ± 1 SE). C-F, Correlations of granzyme B or PD-1 expression on CMV NLV (Fig 3, C and D) and EBV GLC (Fig 3, E and F) pentamer–specific populations with T-cell subset. G, Frequency of PD-1+ NLV+ cells. H, Distribution of NLV+ CD27−/CD28− cells according to CVID status. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig E1 Cytokine production by CD8+ T cells in patients with CVID. A-F, Production of IFN-γ (Fig E1, A and B), TNF-α (Fig E1, C and D), and IL-2 (Fig E1, E and F) by CMV NLV (Fig E1, A, C, and E) or EBV GLC (Fig E1, B, D, and F) peptide–stimulated CD8+ T cells. G-I, Correlation of the frequency of cytokine-producing CD8+ T cells with the frequency of CD27−CD28− NLV pentamer–positive cells (Fig E1, G: IFN-γ; Fig E1, H: TNF-α; and Fig E1, I: IL-2). In Fig E1, A-F, bars indicate mean values. P values for pairwise comparisons are shown for significant differences only. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E2 Analysis of polyfunctional CD8+ T cells. A and C, Frequency (Fig E2, A) and quantity (Fig E2, C) of production of IFN-γ (I), TNF-α (T), IL-2 (L), or combinations thereof by CMV NLV peptide–responsive CD8+ T cells in patients with CVID with (black bars) and without (white bars) inflammation and healthy control subjects (hashed bars). B, Frequency data for EBV GLC–responsive cells. Bars indicate mean percentages ± 1 SEM. Asterisks indicate significantly increased values (P < .0001). Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E3 Proliferation enhancement by stimulated CD8+ T-cell supernatants. A and B, Supernatants (SNT) of proliferating PBMCs from patients with inflammatory (Fig E3, A) but not noninflammatory (Fig E3, B) CVID enhance proliferation of CMV peptide–stimulated PBMCs from patients with noninflammatory CVID (mean ± SE of 4 experiments). Asterisks indicate significantly increased values: (P < .0001). C and D, Enhancement is dose dependent (Fig E3, C), and most proliferating cells are CMV NLV pentamer positive (Fig E3, D). E-G, Proliferation is inhibited by anti–IFN-γ and anti–TNF-α antibodies and enhanced by exogenous IFN-γ and TNF-α (data from representative experiments). In panel G, black bars: cytokine addition; white bars: no cytokine addition. CFSE, Carboxyfluorescein diacetate succinimidyl ester. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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