Cutting Edge:Transcriptional profiling reveals multifunctional and cytotoxic antiviral responses of zika virus-specific CD8+ T cells

Alba Grifoni, Priscilla Costa-Ramos, John Pham, Yuan Tian, Sandy L. Rosales, Grégory Seumois, John Sidney, Aruna D. De Silva, Lakshmanane Premkumar, Matthew H. Collins, Mars Stone, Phillip J. Norris, Claudia M.E. Romero, Anna P Durbin, Michael J. Ricciardi, Julie E. Ledgerwood, Aravinda M. De Silva, Michael Busch, Bjoern Peters, Pandurangan VijayanandEva Harris, Andrew K. Falconar, Esper Kallas, Daniela Weiskopf, Alessandro Sette

Research output: Contribution to journalArticle

Abstract

Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKVspecific CD8+ T cells are characterized by a polyfunctional IFN-g signature with upregulation of TNF-a, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection. The Journ Al of Immunology, 2018, 201: 3487-3491.

Original languageEnglish (US)
Pages (from-to)3487-3491
Number of pages5
JournalJournal of Immunology
Volume201
Issue number12
DOIs
StatePublished - Dec 15 2018
Externally publishedYes

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Antiviral Agents
T-Lymphocytes
Up-Regulation
Dengue Virus
Tumor Necrosis Factor Receptors
Allergy and Immunology
Immunity
Flow Cytometry
Public Health
Phenotype
Zika Virus
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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Cutting Edge:Transcriptional profiling reveals multifunctional and cytotoxic antiviral responses of zika virus-specific CD8+ T cells. / Grifoni, Alba; Costa-Ramos, Priscilla; Pham, John; Tian, Yuan; Rosales, Sandy L.; Seumois, Grégory; Sidney, John; De Silva, Aruna D.; Premkumar, Lakshmanane; Collins, Matthew H.; Stone, Mars; Norris, Phillip J.; Romero, Claudia M.E.; Durbin, Anna P; Ricciardi, Michael J.; Ledgerwood, Julie E.; De Silva, Aravinda M.; Busch, Michael; Peters, Bjoern; Vijayanand, Pandurangan; Harris, Eva; Falconar, Andrew K.; Kallas, Esper; Weiskopf, Daniela; Sette, Alessandro.

In: Journal of Immunology, Vol. 201, No. 12, 15.12.2018, p. 3487-3491.

Research output: Contribution to journalArticle

Grifoni, A, Costa-Ramos, P, Pham, J, Tian, Y, Rosales, SL, Seumois, G, Sidney, J, De Silva, AD, Premkumar, L, Collins, MH, Stone, M, Norris, PJ, Romero, CME, Durbin, AP, Ricciardi, MJ, Ledgerwood, JE, De Silva, AM, Busch, M, Peters, B, Vijayanand, P, Harris, E, Falconar, AK, Kallas, E, Weiskopf, D & Sette, A 2018, 'Cutting Edge:Transcriptional profiling reveals multifunctional and cytotoxic antiviral responses of zika virus-specific CD8+ T cells', Journal of Immunology, vol. 201, no. 12, pp. 3487-3491. https://doi.org/10.4049/jimmunol.1801090
Grifoni, Alba ; Costa-Ramos, Priscilla ; Pham, John ; Tian, Yuan ; Rosales, Sandy L. ; Seumois, Grégory ; Sidney, John ; De Silva, Aruna D. ; Premkumar, Lakshmanane ; Collins, Matthew H. ; Stone, Mars ; Norris, Phillip J. ; Romero, Claudia M.E. ; Durbin, Anna P ; Ricciardi, Michael J. ; Ledgerwood, Julie E. ; De Silva, Aravinda M. ; Busch, Michael ; Peters, Bjoern ; Vijayanand, Pandurangan ; Harris, Eva ; Falconar, Andrew K. ; Kallas, Esper ; Weiskopf, Daniela ; Sette, Alessandro. / Cutting Edge:Transcriptional profiling reveals multifunctional and cytotoxic antiviral responses of zika virus-specific CD8+ T cells. In: Journal of Immunology. 2018 ; Vol. 201, No. 12. pp. 3487-3491.
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AU - Grifoni, Alba

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AU - Tian, Yuan

AU - Rosales, Sandy L.

AU - Seumois, Grégory

AU - Sidney, John

AU - De Silva, Aruna D.

AU - Premkumar, Lakshmanane

AU - Collins, Matthew H.

AU - Stone, Mars

AU - Norris, Phillip J.

AU - Romero, Claudia M.E.

AU - Durbin, Anna P

AU - Ricciardi, Michael J.

AU - Ledgerwood, Julie E.

AU - De Silva, Aravinda M.

AU - Busch, Michael

AU - Peters, Bjoern

AU - Vijayanand, Pandurangan

AU - Harris, Eva

AU - Falconar, Andrew K.

AU - Kallas, Esper

AU - Weiskopf, Daniela

AU - Sette, Alessandro

PY - 2018/12/15

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N2 - Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKVspecific CD8+ T cells are characterized by a polyfunctional IFN-g signature with upregulation of TNF-a, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection. The Journ Al of Immunology, 2018, 201: 3487-3491.

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