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Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells  Yifang Gao, PhD, Sarita Workman, MSc,

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Presentation on theme: "Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells  Yifang Gao, PhD, Sarita Workman, MSc,"— Presentation transcript:

1 Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells  Yifang Gao, PhD, Sarita Workman, MSc, Stephan Gadola, MD, PhD, Tim Elliott, PhD, Bodo Grimbacher, MD, Anthony P. Williams, MRCP, FRCPath, PhD  Journal of Allergy and Clinical Immunology  Volume 133, Issue 5, Pages e1 (May 2014) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Enumeration of iNKT cells in patients with CVID and healthy controls in whole blood. A, FACS analysis for stepwise iNKT cell enumeration subgating T cells for Vα24 and Vβ11 expression to identify the number of iNKT cells. CD4 and CD8 coreceptor expression in iNKT cells and Vα24 non-iNKT cells is shown to highlight the distinctive coreceptor expression of iNKT cells and conventional T cells. B, Comparison of iNKT cell number in all 36 patients with CVID and controls. C, A longitudinal assessment of iNKT cells in patients with CVID showing a stability of their iNKT enumeration. FACS, Fluorescence-activated cell sorting. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Phenotypic analysis of iNKT cells in patients with CVID and controls. A, CD161 MFI expression by iNKT cells in patients with CVID and controls. B, Presence of CD4:non-CD4 iNKT cells in patients with CVID and controls. MFI, Mean fluorescent intensity. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Proliferation of iNKT cells in patients with CVID and controls. A, Representative FACS profile of iNKT cells preproliferation and postproliferation on day 7 in a representative healthy control. B, Representative FACS profiles of iNKT cells preproliferation and postproliferation in 2 patients with CVID representative of those with and without detectable baseline iNKT cells. C, Fold increase in proliferation of iNKT cells in group 1 (28/36) and group 2 (8/36) patients with CVID and normal controls. FACS, Fluorescence-activated cell sorting. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Enumeration and function of iNKT cells in XLA. A, Representative FACS plot for 1 of 4 patients with XLA together with a representative patient with CVID and healthy control. B, Enumeration of iNKT cells in 4 patients with XLA and controls. C, Representative FACS plot of iNKT cells preproliferation and postproliferation in a patient with XLA. D, Fold increase in the proliferation of iNKT cells in patients with XLA and controls. FACS, Fluorescence-activated cell sorting. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 iNKT cell cytokine productions in response to α-GalCer. A, ELISPOT IFN-γ production from 3 patients with CVID in group 2 and the mean of 16 controls. B, ELISPOT IL-17 production from 3 patients with CVID in group 2 and the mean of 16 controls. C, ELISPOT IL-13 production from 3 patients with CVID in group 2 and the mean of 16 controls. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Association of iNKT cells and B-cell subsets. A, Relationship between the number of iNKT cells and the B-cell class-switched memory compartment. B, Relationship between the number of iNKT cells and CD21−CD38− B-cell subset. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E1 Comparison of CD1d tetramer and invariant TCR approaches for iNKT cell identification. A, Representative FACS profile of iNKT cells identified by using a CD1d tetramer and invariant TCR antibodies in controls and patients with CVID (groups 1 and 2). B, Quantification of iNKT cells enumerated with tetramer and invariant TCR techniques in a cohort of 10 patients with CVID (labeled as P1-P10) and 4 healthy controls (labeled as C1-C4). FACS, Fluorescence-activated cell sorting. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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