Presentation is loading. Please wait.

Presentation is loading. Please wait.

CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis  Esther Morel, PhD, Salvador Escamochero,

Published byAmberlynn White Modified over 5 years ago

Similar presentations

Presentation on theme: "CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis  Esther Morel, PhD, Salvador Escamochero,"— Presentation transcript:

1 CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis  Esther Morel, PhD, Salvador Escamochero, BS, Rosario Cabañas, MD, PhD, Rosa Díaz, MD, PhD, Ana Fiandor, MD, Teresa Bellón, PhD  Journal of Allergy and Clinical Immunology  Volume 125, Issue 3, Pages e8 (March 2010) DOI: /j.jaci Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 HLA-E expression in affected skin. A, Flow cytometric analysis of HLA-I (solid histograms) and HLA-E (open histograms) expression in keratinocytes from a representative patient with MPE and a healthy donor (HD). B, Mean fluorescence intensity (MFI) of HLA-I and HLA-E expression in keratinocytes from 5 healthy donors (HD) and 8 patients (P). Horizontal bars correspond to the mean values. C, Immunoperoxidase staining of HLA-E in skin biopsy specimens from 3 patients. Original magnification 200× (panels a-f) and 400× (panels g-h). Arrowheads in panel h show specific staining in keratinocytes within necrotic skin. D, Immunoblot analysis of soluble HLA-E (sHLA-E) in fluids and sera from acute or resolution samples in 3 representative patients with SJS/TEN, healthy donors, and patients with mechanical trauma (MT). Culture supernatants from the HLA-I− cell line and its HLA-E transfectant, 221.AEH, were used as negative and positive controls. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Cytotoxic lymphocytes are activated by HLA-E in peripheral blood and blister fluid from patients with SJS/TEN. A, 51Cr release assays showing lysis of PBMCs from healthy donors and patients with MPE and SJS/TEN against the and 221.AEH cell lines. Means and SEMs of independent experiments are shown. B and C, BFCs from patients with SJS/TEN were used as effector cells in 51Cr release assays. Fig 2, B, Mean values and SEMs of percentages of lysis against and 221.AEH cells. Fig 2, C, Lysis of primary allogenic keratinocytes (KC) pretreated or not with IFN-γ by BFCs from 2 representative patients. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 CD94/NKG2C expression in lymphocytes or blasts from patients with SJS/TEN. A, Frequencies of CD94/NKG2C+ cells in CD3+CD8+, CD3+CD8−, and CD3− peripheral blood lymphocytes from 3 representative acute samples (SJS8, SJS2, and TEN2) and 1 resolution sample (TEN2 resolution). B, Frequencies of CD94/NKG2C+ cells in blister lymphocytes or blasts in 3 representative patients. PerCP, Peridinin-chlorophyll-protein. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 CD94/NKG2C expression on peripheral blood lymphocytes and blasts from patients with SJS/TEN. A, Frequencies of CD94/NKG2C+ cells in peripheral blood lymphocytes or blast subpopulations in acute samples from patients with SJS/TEN. B, Frequencies of CD94/NKG2C+ cells in peripheral blood lymphocyte (L) or blast (B) subpopulations in acute and resolution samples from 3 patients with SJS/TEN. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Peripheral blood NK and T lymphocytes from patients with SJS/TEN recognize HLA-E through the activating receptor CD94/NKG2C. A, Cytotoxicity mediated by PBMCs from patients' acute samples and samples from healthy donors against and 221.AEH cell lines in the presence or absence of blocking anti-NKG2C mAbs. Means and SEMs of independent experiments carried out with 3 patients with SJS are shown. B, CD107a mobilization assays. Graphs show the percentage of CD107a+ cells in CD3+ or CD3− lymphocyte subpopulations expressing or not CD94/NKG2C in a representative patient with SJS on coculture with and 221.AEH cell lines. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 CD94/NKG2C-dependent degranulation in blister lymphocytes. A and B, BFCs from patients SJS6 and SJS4 were cultured alone or with and 221.AEH cells in the absence or presence of anti-NKG2C mAbs. Fig 6, A, shows percentages of CD3+CD8+CD107a+ lymphocytes in a representative experiment. Fig 6, B, CD3−CD107a+ blister fluid lymphocytes in patient SJS6 after coculture in the absence or presence of or 221.AEH cells and blocking anti-NKG2C mAbs. C, Induction of surface CD107a in total and CD3− BFCs from patient SJS4 after coculture in the absence or presence of autologous keratinocytes (KC) pretreated or not with IFN-γ and with or without specific anti-NKG2C mAbs. Mean percentages of CD107a+ lymphocytes in triplicate cultures are shown. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Flow cytometric analysis of cell-surface receptor expression on T lymphocytes from peripheral blood and blister fluids from patients with SJS/TEN. Panels show frequencies of CD8+, CD94+, CD56+, KIR2DL2/L3/S2+, HLA-DR+, and CD25+ cells in CD3+ blister fluid and peripheral blood lymphocytes from acute and resolution samples in a representative patient with TEN. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 FasL and IFN-γ levels in sera and blister fluids from patients with SJS/TEN. Graphs show picograms of FasL and IFN-γ per milliliter of serum or blister fluid from patients' acute samples and healthy donors (HD). Horizontal bars correspond to mean values. ∗P value, Wilcoxon matched pair test; #P value, Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 HLA -E–specific CD56+CD8+ T-cell clones are cytotoxic against IFN-γ–stimulated keratinocytes expressing HLA-E. A, HLA-I and HLA-E expression in primary keratinocytes and HaCaT cells stimulated or not with IFN-γ. Staining with control IgG1 and specific mAbs is shown. B and C, Cytotoxicity mediated by CD56+CD8+ T-cell clones against HaCaT keratinocytes pretreated or not with IFN-γ. The cell line and its HLA-E transfectant, 221.AEH, were used as negative and positive controls, respectively. Fig E3, B, Percentages of lysis from 3 representative clones of 5 tested. Fig E3, C, Lysis in the presence of anti HLA-E and anti-HLA-I mAbs. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Flow cytometric analysis of receptor expression in PBMCs
Flow cytometric analysis of receptor expression in PBMCs. A, Percentages of CD94+, CD94/NKG2A+, and CD94/NKG2C+ cells in CD3+ and CD3− peripheral blood lymphocytes from patients with SJS/TEN (acute samples) and healthy donors (HD). B, Percentages of CD94/NKG2C+ cells (means ± SEMs) in CD3+CD8+ and CD3− peripheral blood lymphocytes from acute samples in patients with SJS/TEN and MPE . ∗P value, Wilcoxon matched pair test; #P value, Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 CD94/NKG2C expression on peripheral blood lymphocytes and blasts in acute and resolution samples from patients with drug-induced cutaneous reactions. A, CD3 and CD8 expression and forward scatter (FSC) analysis in total PBMCs from a representative patient. Red- and blue-colored populations correspond to lymphocytes and blasts, respectively. B, Panels show percentages of CD3+CD8+, CD94/NKG2C+, and CD3−CD94/NKG2C+ cells in peripheral blood lymphocytes (red gates) or blasts (blue gates) in 3 patients. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

13 Journal of Allergy and Clinical Immunology 2010 125, 703-710
Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis  Esther Morel, PhD, Salvador Escamochero,"

Similar presentations

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis  Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis  Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.
Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders  Annick A.J.M.

Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders  Annick A.J.M.
Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong Th17/Th1 T-cell responses  Anja Hänsel,

Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong Th17/Th1 T-cell responses  Anja Hänsel,
Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu  Amanda J. Reefer, MS, Kathryn.

Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu  Amanda J. Reefer, MS, Kathryn.
Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production  Laura Maggi, PhD, Gianni Montaini, BSc, Alessio Mazzoni,

Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production  Laura Maggi, PhD, Gianni Montaini, BSc, Alessio Mazzoni,
Potential role of extracellular vesicle–mediated antigen presentation in Helicobacter pylori hypersensitivity during eradication therapy  Takamasa Ito,

Potential role of extracellular vesicle–mediated antigen presentation in Helicobacter pylori hypersensitivity during eradication therapy  Takamasa Ito,
Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy  Yin Yao, MD, Cai-Ling.

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy  Yin Yao, MD, Cai-Ling.
Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites 

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites 
Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection 

Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection 
Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response  Miriam Wittmann, MD, Mareike Alter, Tanja.

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response  Miriam Wittmann, MD, Mareike Alter, Tanja.
IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation  Regina K. Rowe, MD, PhD, David M. Pyle, MD,

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation  Regina K. Rowe, MD, PhD, David M. Pyle, MD,
Predominance of type 2 cytokine–producing CD4+ and CD8+ cells in patients with atopic dermatitis  Masatoshi Nakazawa, DVMa, Nakako Sugi, MDb, Hiroshi.

Predominance of type 2 cytokine–producing CD4+ and CD8+ cells in patients with atopic dermatitis  Masatoshi Nakazawa, DVMa, Nakako Sugi, MDb, Hiroshi.
Toll-like receptor 7–induced naive human B-cell differentiation and immunoglobulin production  Mark C. Glaum, MD, PhD, Shilpi Narula, MD, Decheng Song,

Toll-like receptor 7–induced naive human B-cell differentiation and immunoglobulin production  Mark C. Glaum, MD, PhD, Shilpi Narula, MD, Decheng Song,
Dual nature of T cell–epithelium interaction in chronic rhinosinusitis

Dual nature of T cell–epithelium interaction in chronic rhinosinusitis
Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation  Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation  Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,
Volume 137, Issue 3, Pages e7 (September 2009)

Volume 137, Issue 3, Pages e7 (September 2009)
Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL- 5 and IL-5 receptor levels  Miguel L. Stein, MD, Joyce M. Villanueva,

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL- 5 and IL-5 receptor levels  Miguel L. Stein, MD, Joyce M. Villanueva,
Type 2 innate lymphoid cells in induced sputum from children with severe asthma  Prasad Nagakumar, MBBS, Laura Denney, PhD, Louise Fleming, MD, Andrew.

Type 2 innate lymphoid cells in induced sputum from children with severe asthma  Prasad Nagakumar, MBBS, Laura Denney, PhD, Louise Fleming, MD, Andrew.
Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization  Silvia.

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization  Silvia.
Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis  Hari Balaji, MSc, Annice Heratizadeh,

Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis  Hari Balaji, MSc, Annice Heratizadeh,

Similar presentations

Ads by Google