Dynamic regulation of functionally distinct virus-specific T cells

Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3669-74. doi: 10.1073/pnas.0915168107. Epub 2010 Feb 4.


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-gamma, TNF-alpha, MIP1beta, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen Presentation
  • Antigens, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunodominant Epitopes / immunology*
  • Immunoglobulins / immunology
  • Lymphocyte Activation*
  • Peptides / immunology
  • Viral Matrix Proteins / immunology


  • Antigens, Viral
  • HLA-A2 Antigen
  • Immunodominant Epitopes
  • Immunoglobulins
  • M1 protein, Influenza A virus
  • Peptides
  • Viral Matrix Proteins