Inflammation in common variable immunodeficiency is associated with a distinct CD8+ response to cytomegalovirus Sayed Mahdi Marashi, PhD, Mohammad Raeiszadeh,

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Presentation transcript:

Inflammation in common variable immunodeficiency is associated with a distinct CD8+ response to cytomegalovirus Sayed Mahdi Marashi, PhD, Mohammad Raeiszadeh, MSc, Sarita Workman, MSc, Afsar Rahbar, PhD, Cecilia Soderberg-Naucler, PhD, Paul Klenerman, PhD, Ronnie Chee, MBBS, A. David Webster, MD, Richard S.B. Milne, PhD, Vincent C. Emery, PhD Journal of Allergy and Clinical Immunology Volume 127, Issue 6, Pages 1385-1393.e4 (June 2011) DOI: 10.1016/j.jaci.2011.04.001 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A, Percentage of CMV (NLV) or EBV (GLC) pentamer+ cells in patients with CVID or healthy controls. B and D, Data from A showing inflammatory and noninflammatory groups. C, Frequency of CMV (NLV) pentamer+ cells in serial samples from 4 patients (Pt). Lines in A, B, and D indicate means. Journal of Allergy and Clinical Immunology 2011 127, 1385-1393.e4DOI: (10.1016/j.jaci.2011.04.001) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Phenotyping of CMV NLV–specific CD8+ T cells. A and B, PD-1 (median fluorescence intensity [MFI]). C and D, Ki-67. E and F, HLA-DR. G and H, CD73. Bars indicate mean percentage values. Journal of Allergy and Clinical Immunology 2011 127, 1385-1393.e4DOI: (10.1016/j.jaci.2011.04.001) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Proliferation of CMV-specific CD8+ T cells. A, Representative fluorescence-activated cell sorting plots. B and C, Analysis of inflammatory (n = 6) and noninflammatory (n = 8) samples. Insert in B shows generational analysis after NLV stimulation. D, Mixed peptide stimulation. E, Specificity (CMV, black; EBV, white) of expanded cells from D. Data obtained 5 days after stimulation. PHA, Phytohemagglutinin; Stim, stimulation. Journal of Allergy and Clinical Immunology 2011 127, 1385-1393.e4DOI: (10.1016/j.jaci.2011.04.001) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Immunohistochemical detection of CMV antigens. Colon tissue from representative patient with inflammatory CVID (A, B, E, F, I, J) or healthy control subject (C, D, G, H, K, L) was stained for CMV IEA (A, C, E, G) or LA (B, D, F, H); α-actin (I, K) or processed without primary antibody (J, L). E, F, G, and H are enlargements of areas boxed in A, B, C, and D, respectively. Brown staining (diaminobenzidine chromogen) indicates presence of antigen. Original magnification ×40 (A and B); ×20 (C, D, I-L). Bars are 50 μm. Journal of Allergy and Clinical Immunology 2011 127, 1385-1393.e4DOI: (10.1016/j.jaci.2011.04.001) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Cytokine production and degranulation. A, Proportion of responding CD8+ T cells producing IFN-γ, TNF-α, or both after pp65 peptide pool stimulation. (Means from 19 patients with CVID and 12 healthy controls.) B, Frequency of double producers (DP) among total CD8+ cells. C, Percentage of double producers that degranulated. Bars in B and C indicate means. Journal of Allergy and Clinical Immunology 2011 127, 1385-1393.e4DOI: (10.1016/j.jaci.2011.04.001) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Phenotyping of CMV NLV–specific CD8+ T cells. A and B, PD-1 (frequency). C, Representative fluorescence-activated cell sorting plots for anti–Ki-67 and isotype control staining on CMV NLV pentamer+ CD8+ T cells. D and E, CD57 (frequency). Bars in A, B, D, and E indicate mean percentage values. PE, Phycoerythrin. Journal of Allergy and Clinical Immunology 2011 127, 1385-1393.e4DOI: (10.1016/j.jaci.2011.04.001) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 High-avidity CMV NLV–specific CD8+ cells in inflammatory CVID. A and C, Representative fluorescence-activated cell sorting plots of normal and null tetramer staining for an inflammatory (A) and a noninflammatory patient (C). B and D, Bar graphs showing the percentage of total CD8+ T cells recognized by the normal (black) and null (white) tetramers in patients with inflammatory (B) and noninflammatory (D) CVID. Journal of Allergy and Clinical Immunology 2011 127, 1385-1393.e4DOI: (10.1016/j.jaci.2011.04.001) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions