Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types

J Leukoc Biol. 2010 Jul;88(1):69-78. doi: 10.1189/jlb.1209816. Epub 2010 Mar 30.


This study tested the hypothesis that individual myeloid subsets have a differential ability to maintain memory CD8 T cells via IL-15. Although DCs support IL-15-mediated homeostasis of memory CD8 T cells in vivo, whether various DC subsets and other myeloid cells similarly mediate homeostasis is unknown. Therefore, we studied the ability of different myeloid cells to maintain memory CD8 T cells in vitro. Using an in vitro cocoulture system that recapitulated known roles of DCs and IL-15 on memory CD8 T cells, all in vitro-derived or ex vivo-isolated DCs maintained CD8 T cells better than rIL-15 alone, and FLT-3L-DCs are the most efficient compared with GM-DCs, BM-derived macrophages, or freshly isolated DCs. Although FLT-3L-DCs were the least effective at inducing CD8 T cell proliferation, FLT-3L-DCs promoted better CD8 T cell survival and increased Bcl-2 and MCL-2 expression in CD8 T cells. T cell maintenance correlated only partially with DC expression of IL-15Ralpha and IL-15, suggesting that DCs provided additional support signals. Indeed, in the absence of IL-15 signals, CD70/CD27 further supported CD8 T cell maintenance. IFN-alpha enhanced CD70 expression by DCs, resulting in increased proliferation of CD8 T cells. Overall, this study supports our hypothesis by demonstrating that specific DC subtypes had a greater capacity to support memory CD8 T cell maintenance and did so through different mechanisms. Furthermore, this study shows that IL-15 trans-presentation can work in conjunction with other signals, such as CD70/CD27 interactions, to mediate CD8 T cell homeostasis efficiently.

Publication types

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

MeSH terms

  • Animals
  • CD27 Ligand / physiology
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Proliferation
  • Cell Survival
  • Dendritic Cells / physiology*
  • Immunologic Memory*
  • Interferon-alpha / pharmacology
  • Interleukin-15 Receptor alpha Subunit / physiology
  • Interleukin-5 / pharmacology
  • Macrophages / physiology*
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology


  • CD27 Ligand
  • Interferon-alpha
  • Interleukin-15 Receptor alpha Subunit
  • Interleukin-5
  • Membrane Proteins
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • flt3 ligand protein