Presentation is loading. Please wait.

Presentation is loading. Please wait.

Jelle de Wit, PhD, Maarten E. Emmelot, BSc, Martien C. M

Published byLewis Wiggins Modified over 6 years ago

Similar presentations

Presentation on theme: "Jelle de Wit, PhD, Maarten E. Emmelot, BSc, Martien C. M"— Presentation transcript:

1 Mumps infection but not childhood vaccination induces persistent polyfunctional CD8+ T-cell memory 
Jelle de Wit, PhD, Maarten E. Emmelot, BSc, Martien C.M. Poelen, BSc, Rob S. van Binnendijk, PhD, Saskia van der Lee, MSc, Debbie van Baarle, PhD, Wanda G.H. Han, PhD, Cécile A.C.M. van Els, PhD, Patricia Kaaijk, PhD  Journal of Allergy and Clinical Immunology  Volume 141, Issue 5, Pages e12 (May 2018) DOI: /j.jaci Copyright © 2018 The Authors Terms and Conditions

2 Fig 1 MuV-specific IFN-γ production by T cells from mumps cases. PBMCs from mumps cases at various time points after disease onset, or from healthy vaccinees, were depleted of CD56+ cells and stimulated in vitro with live MuV for 24 hours. A, The frequency of IFN-γ–producing cells was analyzed by ELISpot. Longitudinal mumps cases followed for 3 years are shown in red. B-E, Total PBMCs derived from 7 mumps cases (Fig 1, B-D) and 5 healthy vaccinees (Fig 1, E) were stimulated with live MuV for 24 hours and IFN-γ–producing cells were analyzed by intracellular cytokine staining. F and G, Absolute numbers of IFN-γ−producing CD8+ T cells (Fig 1, F) and NK cells (Fig 1, G) were calculated on the basis of the number of isolated PBMCs per milliliter of whole blood. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

3 Fig 2 IFN-γ, CD107a, TNF, and IL-2 expression by MuV-specific CD8+ T cells differs between mumps cases and vaccinees. A, Total PBMCs derived from mumps cases or healthy individuals were stimulated with live MuV for 24 hours and MuV-specific CD8+ T cells were determined by CD137 expression. B-E, Cytokine production (IFN-γ/TNF/IL-2) and CD107a expression within activated CD137+CD8+ T cells are presented in bar graphs and combined in pie charts (insert). Data are from 6 mumps cases and 6 healthy vaccinees, combined in Fig E6. F, The MuV-specific cellular IFN-γ response 1 month after vaccination of 9-year-old children. G, Frequencies of CD137+CD8+ cells expressing 1 or more of 4 markers 1 month after vaccination. Data are from 4 to 5 vaccinees. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

4 Fig E1 CD56 depletion lowers IFN-γ responses of late time-point samples. Cryopreserved PBMCs of mumps cases (n = 3) were thawed and depleted of CD56+ cells (CD56−depleted) or not (PBMCs) and stimulated with live Jeryl Lynn MuV. IFN-γ−producing cells were analyzed by ELISpot after 24 hours. Results shown are the mean + SD from 3 mumps cases 1 to 2 months or 7 to 10 months after disease onset. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

5 Fig E2 MuV-specific CD8+ T cells display CD137 and IFN-γ. Total PBMCs derived from a mumps case 1 to 2 months, 7 to 10 months, or 3 years after disease onset were stimulated with mock or live Jeryl Lynn MuV for 24 hours. Brefeldin A and monensin were added for the last 4 hours. Activation (CD137) and IFN-γ production within CD8+ T cells were determined by flow cytometry. Representative plots are shown from 1 of 7 mumps cases. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

6 Fig E3 MuV-specific CD137+CD8+ T cells produce IFN-γ and TNF and display cytotoxic activity. Total PBMCs longitudinally derived from mumps cases or healthy vaccinees were stimulated with live Jeryl Lynn MuV for 24 hours. Expression of activation marker CD137, intracellular cytokines (IFN-γ and TNF), and CD107a within CD8+ T cells was determined by flow cytometry. Representative plots are shown for longitudinal samples from 1 of 7 mumps cases and 1 of 5 vaccinees. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

7 Fig E4 MuV-specific activation is mainly displayed by Temra and Tem CD8+ cells. Total PBMCs derived from 7 mumps cases were stimulated with live Jeryl Lynn MuV for 24 hours. Expression of activation marker CD137 within CD8+ T cells was determined by flow cytometry. The proportions of cells with a naive (Tn-like; CD45RO−CCR7+), central memory (Tcm; CD45RO+CCR7+), Tem (CD45RO+CCR7−), and Temra (CD45RO−CCR7−) phenotype within the activated, CD137-expressing CD8+ T cells were determined. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

8 Fig E5 IFN-γ, CD107a, TNF, and IL-2 expression by MuV-specific CD8+ T cells. Total PBMCs derived from mumps cases or healthy vaccinees were stimulated with live MuV for 24 hours. Cytokine production (IFN-γ, TNF, and IL-2) and CD107a expression within activated CD137+CD8+ T cells were determined by flow cytometry. Data are from 6 to 7 mumps cases and 6 healthy vaccinees. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

9 Fig E6 IFN-γ, CD107a, TNF, and IL-2 expression from MuV-activated CD137+CD8+ T cells. Total PBMCs derived from mumps cases 1 to 2 months, 7 to 10 months, or 3 years after disease onset, or healthy vaccinees were stimulated with live Jeryl Lynn MuV for 24 hours. Cytokine production (IFN-γ, TNF, and IL-2) and CD107a expression within activated CD137+CD8+ T cells were determined by flow cytometry. Data shown are mean (as indicated) + SD from responses at longitudinal time points from 6 mumps cases and from 6 vaccinees. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

10 Fig E7 MuV-specific CD8+ T cells show comparable polyfunctionality. Total PBMCs derived from previously vaccinated (left panels; n = 3) or unvaccinated (right; n = 3) mumps cases were stimulated with live MuV for 24 hours. Cytokine production (IFN-γ, TNF, and IL-2) and CD107a expression within activated CD137+CD8+ T cells were determined by flow cytometry. Frequencies of CD137+CD8+ cells expressing 1 or more of 4 markers are presented in bar graphs and combined in pie charts (insert). Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

11 Fig E8 MuV-specific IFN-γ production from vaccinated children. Total PBMCs derived from 5 children receiving a second, booster MMR vaccination were stimulated with live MuV for 24 hours and IFN-γ–producing cells were determined by intracellular cytokine staining. The 1-month postvaccination data are depicted in Fig 2, G. Because of the low number, Tem/Temra could not be identified. Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

12 Fig E9 MuV-specific CD8+CD137+ T cells show no polyfunctionality after MMR-2 vaccination in children. Total PBMCs derived from 4 children receiving their second MMR vaccination were stimulated with live MuV for 24 hours and cytokine production (IFN-γ, TNF, and IL-2) and CD107a expression within activated CD137+CD8+ T cells were determined by flow cytometry. Frequencies of CD137+CD8+ cells expressing 1 or more of 4 markers are presented in bar graphs and combined in pie charts (insert). Journal of Allergy and Clinical Immunology  , e12DOI: ( /j.jaci ) Copyright © 2018 The Authors Terms and Conditions

Download ppt "Jelle de Wit, PhD, Maarten E. Emmelot, BSc, Martien C. M"

Similar presentations

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy  Erik Wambre, PhD, Jonathan.

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy  Erik Wambre, PhD, Jonathan.
Identification of drug- and drug-metabolite immune responses originating from both naive and memory T cells  Andrew Gibson, MRes, Lee Faulkner, PhD, Sally.

Identification of drug- and drug-metabolite immune responses originating from both naive and memory T cells  Andrew Gibson, MRes, Lee Faulkner, PhD, Sally.
Volume 66, Issue 6, Pages (June 2013)

Volume 66, Issue 6, Pages (June 2013)
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.
Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion 

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion 
Defective natural killer–cell cytotoxic activity in NFKB2-mutated CVID-like disease  Vassilios Lougaris, MD, Giovanna Tabellini, PhD, Massimiliano Vitali,

Defective natural killer–cell cytotoxic activity in NFKB2-mutated CVID-like disease  Vassilios Lougaris, MD, Giovanna Tabellini, PhD, Massimiliano Vitali,
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,
Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood  Glynis Frans, MPharm, Leen Moens, PhD, Heidi.

Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood  Glynis Frans, MPharm, Leen Moens, PhD, Heidi.
Regulatory T cells as a biomarker for response to adalimumab in rheumatoid arthritis  Dao X. Nguyen, BSc, Alice Cotton, RN, BSc, Laura Attipoe, MBBS, Coziana.

Regulatory T cells as a biomarker for response to adalimumab in rheumatoid arthritis  Dao X. Nguyen, BSc, Alice Cotton, RN, BSc, Laura Attipoe, MBBS, Coziana.
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 
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,
A novel mutation in CD132 causes X-CID with defective T-cell activation and impaired humoral reactivity  Taco W. Kuijpers, MD, PhD, Paul A. Baars, PhD,

A novel mutation in CD132 causes X-CID with defective T-cell activation and impaired humoral reactivity  Taco W. Kuijpers, MD, PhD, Paul A. Baars, PhD,
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.
Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures  Jelle de Wit, PhD, Tineke Jorritsma,

Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures  Jelle de Wit, PhD, Tineke Jorritsma,
CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion  Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion  Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.
Immunologic defects in 22q11.2 deletion syndrome

Immunologic defects in 22q11.2 deletion syndrome
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,
Rapamycin preferentially inhibits human IL-5+ TH2-cell proliferation via an mTORC1/S6 kinase-1–dependent pathway  Yuzhi Yin, MD, PhD, Alyssa Mitson-Salazar,

Rapamycin preferentially inhibits human IL-5+ TH2-cell proliferation via an mTORC1/S6 kinase-1–dependent pathway  Yuzhi Yin, MD, PhD, Alyssa Mitson-Salazar,
T-cell regulation during viral and nonviral asthma exacerbations

T-cell regulation during viral and nonviral asthma exacerbations
Penicillium marneffei infection and impaired IFN-γ immunity in humans with autosomal- dominant gain-of-phosphorylation STAT1 mutations  Pamela P.W. Lee,

Penicillium marneffei infection and impaired IFN-γ immunity in humans with autosomal- dominant gain-of-phosphorylation STAT1 mutations  Pamela P.W. Lee,

Similar presentations

Ads by Google