Dynamic regulation of functionally distinct virus-specific T cells

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

Keywords

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

ASJC Scopus subject areas

  • General

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