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

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Presentation transcript:

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 1908-1911.e12 (May 2018) DOI: 10.1016/j.jaci.2017.11.047 Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions

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 2018 141, 1908-1911.e12DOI: (10.1016/j.jaci.2017.11.047) Copyright © 2018 The Authors Terms and Conditions