Dynamic regulation of functionally distinct virus-specific T cells

Zaza M. Ndhlovu, Mathias Oelke, Jonathan P Schneck, Diane Griffin

Research output: Contribution to journalArticle

Abstract

The functional capacities of CD8+ T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4+ T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with long-term protection, however, it is still unknown how to stimulate T cells to achieve these responses. To study this, we examined the phenotypes and functions of CD8+ T cells specific for two different virus antigens stimulated ex vivo using either autologous monocyte-derived dendritic cells (moDCs) or HLA-A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus and measles virus tetramer-positive cells were generated by stimulation with peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2, IFN-γ, TNF-α, MIP1β, and CD107a, showed that aAPC-generated CD8+ T cells were multifunctional, whereas moDC-generated cells were mostly monofunctional. aAPC-generated cells also produced more of each cytokine per cell than CD8+ T cells generated with moDCs. These phenotypes were not fixed, as changing the culture conditions of expanding T cells from aAPCs to moDCs, and moDCs to aAPCs, reversed the phenotypes. We conclude that CD8+ T cells are heterogeneous in their functionality and that this is dependent, in a dynamic way, on the stimulating APC. These studies will lead to understanding the factors that influence induction of optimal CD8+ T cell function.

Original languageEnglish (US)
Pages (from-to)3669-3674
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number8
DOIs
StatePublished - Feb 23 2010

Fingerprint

Viruses
T-Lymphocytes
Dendritic Cells
Monocytes
Antigen-Presenting Cells
Phenotype
HLA-A2 Antigen
Measles virus
Orthomyxoviridae
Interleukin-2
Research Personnel
Cytokines
Antigens
Peptides

Keywords

  • Antigen presenting cells
  • CD8 T cells
  • Multifunctional T cells
  • Viral immunity

ASJC Scopus subject areas

  • General

Cite this

Dynamic regulation of functionally distinct virus-specific T cells. / Ndhlovu, Zaza M.; Oelke, Mathias; Schneck, Jonathan P; Griffin, Diane.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 8, 23.02.2010, p. 3669-3674.

Research output: Contribution to journalArticle

@article{d211d69fdcdb472c898e9c091cdb4481,
title = "Dynamic regulation of functionally distinct virus-specific T cells",
abstract = "The functional capacities of CD8+ T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4+ T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with long-term protection, however, it is still unknown how to stimulate T cells to achieve these responses. To study this, we examined the phenotypes and functions of CD8+ T cells specific for two different virus antigens stimulated ex vivo using either autologous monocyte-derived dendritic cells (moDCs) or HLA-A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus and measles virus tetramer-positive cells were generated by stimulation with peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2, IFN-γ, TNF-α, MIP1β, and CD107a, showed that aAPC-generated CD8+ T cells were multifunctional, whereas moDC-generated cells were mostly monofunctional. aAPC-generated cells also produced more of each cytokine per cell than CD8+ T cells generated with moDCs. These phenotypes were not fixed, as changing the culture conditions of expanding T cells from aAPCs to moDCs, and moDCs to aAPCs, reversed the phenotypes. We conclude that CD8+ T cells are heterogeneous in their functionality and that this is dependent, in a dynamic way, on the stimulating APC. These studies will lead to understanding the factors that influence induction of optimal CD8+ T cell function.",
keywords = "Antigen presenting cells, CD8 T cells, Multifunctional T cells, Viral immunity",
author = "Ndhlovu, {Zaza M.} and Mathias Oelke and Schneck, {Jonathan P} and Diane Griffin",
year = "2010",
month = "2",
day = "23",
doi = "10.1073/pnas.0915168107",
language = "English (US)",
volume = "107",
pages = "3669--3674",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - Dynamic regulation of functionally distinct virus-specific T cells

AU - Ndhlovu, Zaza M.

AU - Oelke, Mathias

AU - Schneck, Jonathan P

AU - Griffin, Diane

PY - 2010/2/23

Y1 - 2010/2/23

N2 - The functional capacities of CD8+ T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4+ T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with long-term protection, however, it is still unknown how to stimulate T cells to achieve these responses. To study this, we examined the phenotypes and functions of CD8+ T cells specific for two different virus antigens stimulated ex vivo using either autologous monocyte-derived dendritic cells (moDCs) or HLA-A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus and measles virus tetramer-positive cells were generated by stimulation with peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2, IFN-γ, TNF-α, MIP1β, and CD107a, showed that aAPC-generated CD8+ T cells were multifunctional, whereas moDC-generated cells were mostly monofunctional. aAPC-generated cells also produced more of each cytokine per cell than CD8+ T cells generated with moDCs. These phenotypes were not fixed, as changing the culture conditions of expanding T cells from aAPCs to moDCs, and moDCs to aAPCs, reversed the phenotypes. We conclude that CD8+ T cells are heterogeneous in their functionality and that this is dependent, in a dynamic way, on the stimulating APC. These studies will lead to understanding the factors that influence induction of optimal CD8+ T cell function.

AB - The functional capacities of CD8+ T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4+ T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with long-term protection, however, it is still unknown how to stimulate T cells to achieve these responses. To study this, we examined the phenotypes and functions of CD8+ T cells specific for two different virus antigens stimulated ex vivo using either autologous monocyte-derived dendritic cells (moDCs) or HLA-A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus and measles virus tetramer-positive cells were generated by stimulation with peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2, IFN-γ, TNF-α, MIP1β, and CD107a, showed that aAPC-generated CD8+ T cells were multifunctional, whereas moDC-generated cells were mostly monofunctional. aAPC-generated cells also produced more of each cytokine per cell than CD8+ T cells generated with moDCs. These phenotypes were not fixed, as changing the culture conditions of expanding T cells from aAPCs to moDCs, and moDCs to aAPCs, reversed the phenotypes. We conclude that CD8+ T cells are heterogeneous in their functionality and that this is dependent, in a dynamic way, on the stimulating APC. These studies will lead to understanding the factors that influence induction of optimal CD8+ T cell function.

KW - Antigen presenting cells

KW - CD8 T cells

KW - Multifunctional T cells

KW - Viral immunity

UR - http://www.scopus.com/inward/record.url?scp=77649247346&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649247346&partnerID=8YFLogxK

U2 - 10.1073/pnas.0915168107

DO - 10.1073/pnas.0915168107

M3 - Article

VL - 107

SP - 3669

EP - 3674

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -