Distinct transcriptome profiles of Gag-specific CD8+ T cells temporally correlated with the protection elicited by SIVΔnef live attenuated vaccine

Wuxun Lu, Yanmin Wan, Fangrui Ma, R. Paul Johnson, Qingsheng Li

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: Macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A∗01+ rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in TCR signaling, differentiation and maturation toward central memory cells, with increased expression of CCR7, TCRα, TCRΒ, CD28 and decreased expression of CTLA-4, IFN-γ, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time contributes to the maturation of time-dependent protection.

Original languageEnglish (US)
Article numbere0173929
JournalPloS one
Volume12
Issue number3
DOIs
StatePublished - Mar 2017

Fingerprint

Attenuated Vaccines
T-cells
live vaccines
Transcriptome
transcriptome
Vaccination
T-lymphocytes
vaccination
T-Lymphocytes
Granzymes
Gene expression
Vaccines
Macaca mulatta
Chemokine CCL5
Microarrays
vaccines
gene expression
Blood
Genes
Macaca

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Distinct transcriptome profiles of Gag-specific CD8+ T cells temporally correlated with the protection elicited by SIVΔnef live attenuated vaccine. / Lu, Wuxun; Wan, Yanmin; Ma, Fangrui; Johnson, R. Paul; Li, Qingsheng.

In: PloS one, Vol. 12, No. 3, e0173929, 03.2017.

Research output: Contribution to journalArticle

@article{0c05c91b1da548ae99cbe62046265c49,
title = "Distinct transcriptome profiles of Gag-specific CD8+ T cells temporally correlated with the protection elicited by SIVΔnef live attenuated vaccine",
abstract = "The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: Macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A∗01+ rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in TCR signaling, differentiation and maturation toward central memory cells, with increased expression of CCR7, TCRα, TCRΒ, CD28 and decreased expression of CTLA-4, IFN-γ, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time contributes to the maturation of time-dependent protection.",
author = "Wuxun Lu and Yanmin Wan and Fangrui Ma and Johnson, {R. Paul} and Qingsheng Li",
year = "2017",
month = "3",
doi = "10.1371/journal.pone.0173929",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Distinct transcriptome profiles of Gag-specific CD8+ T cells temporally correlated with the protection elicited by SIVΔnef live attenuated vaccine

AU - Lu, Wuxun

AU - Wan, Yanmin

AU - Ma, Fangrui

AU - Johnson, R. Paul

AU - Li, Qingsheng

PY - 2017/3

Y1 - 2017/3

N2 - The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: Macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A∗01+ rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in TCR signaling, differentiation and maturation toward central memory cells, with increased expression of CCR7, TCRα, TCRΒ, CD28 and decreased expression of CTLA-4, IFN-γ, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time contributes to the maturation of time-dependent protection.

AB - The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: Macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A∗01+ rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in TCR signaling, differentiation and maturation toward central memory cells, with increased expression of CCR7, TCRα, TCRΒ, CD28 and decreased expression of CTLA-4, IFN-γ, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time contributes to the maturation of time-dependent protection.

UR - http://www.scopus.com/inward/record.url?scp=85016155321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016155321&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0173929

DO - 10.1371/journal.pone.0173929

M3 - Article

C2 - 28333940

AN - SCOPUS:85016155321

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e0173929

ER -