Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types.
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.
Frasca
Loredana
L
Department of Immunology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Stonier
Spencer W
SW
Overwijk
Willem W
WW
Schluns
Kimberly S
KS
D000818:Animals; D053282:CD27 Ligand / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival; D003713:Dendritic Cells / Q000502:physiology*; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000494:pharmacology; D053720:Interleukin-15 Receptor alpha Subunit / Q000502:physiology; D015848:Interleukin-5 / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology
D053282:CD27 Ligand; D016898:Interferon-alpha; D053720:Interleukin-15 Receptor alpha Subunit; D015848:Interleukin-5; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C084881:flt3 ligand protein