TY - JOUR
T1 - Cutting Edge:Transcriptional profiling reveals multifunctional and cytotoxic antiviral responses of zika virus-specific CD8 + T cells
AU - Grifoni, Alba
AU - Costa-Ramos, Priscilla
AU - Pham, John
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
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
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) Contracts HHSN272200900042C and HHSN27220140045C, and Grants U19 AI118626-01 to A.S., HHSN268201100001I to M.B., and S10OD016262 to P.V. Further support was provided by the Zika Preparedness Latin American Network, which has received funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement 734584.
PY - 2018/12/15
Y1 - 2018/12/15
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.
AB - 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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U2 - 10.4049/jimmunol.1801090
DO - 10.4049/jimmunol.1801090
M3 - Article
C2 - 30413672
AN - SCOPUS:85058393976
VL - 201
SP - 3487
EP - 3491
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -