CD8(+) T cells sabotage their own memory potential through IFN-gamma-dependent modification of the IL-12/IL-15 receptor alpha axis on dendritic cells Journal Article


Authors: Kohlhapp, F. J.; Zloza, A.; O'Sullivan, J. A.; Moore, T. V.; Lacek, A. T.; Jagoda, M. C.; McCracken, J.; Cole, D. J.; Guevara-Patino, J. A.
Article Title: CD8(+) T cells sabotage their own memory potential through IFN-gamma-dependent modification of the IL-12/IL-15 receptor alpha axis on dendritic cells
Abstract: CD8(+) T cell responses have been shown to be regulated by dendritic cells (DCs) and CD4(+) T cells, leading to the tenet that CD8(+) T cells play a passive role in their own differentiation. In contrast, by using a DNA vaccination model, to separate the events of vaccination from those of CD8(+) T cell priming, we demonstrate that CD8(+) T cells, themselves, actively limit their own memory potential through CD8(+) T cell-derived IFN-gamma-dependent modification of the IL-12/IL-15Ralpha axis on DCs. Such CD8(+) T cell-driven cytokine alterations result in increased T-bet and decreased Bcl-2 expression, and thus decreased memory progenitor formation. These results identify an unrecognized role for CD8(+) T cells in the regulation of their own effector differentiation fate and a previously uncharacterized relationship between the balance of inflammation and memory formation.
Keywords: Humans; Animals; Mice; Mice, Inbred C57BL; Mice, Knockout; Cell Differentiation/immunology; Adoptive Transfer; CD8-Positive T-Lymphocytes/immunology/metabolism; Dendritic Cells/immunology/metabolism; Gene Expression Regulation/immunology; Immunologic Memory; Interferon-gamma; Interleukin-12/genetics/immunology; Interleukin-15/genetics/immunology; Lymphocyte Activation; Melanoma, Experimental/immunology/prevention control; Receptors, Interleukin-12/genetics/immunology; Receptors, Interleukin-15/genetics/immunology; Signal Transduction/immunology; Vaccination; Vaccines, DNA/immunology; Oncology Research Institute
Journal Title: Journal of Immunology
Volume: 188
Issue: 8
ISSN: 1550-6606
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 3639
End Page: 3647
Language: eng
DOI/URL:
Notes: LR: 20130626; GR: 1P01CA154778-01A1/CA/NCI NIH HHS/United States; GR: 5P30CA014599-35/CA/NCI NIH HHS/United States; GR: R21 CA127037/CA/NCI NIH HHS/United States; GR: R21CA127037-01A1/CA/NCI NIH HHS/United States; GR: T32 AI007090/AI/NIAID NIH HHS/United States; JID: 2985117R; 0 (Interleukin-15); 0 (Receptors, Interleukin-12); 0 (Receptors, Interleukin-15); 0 (Vaccines, DNA); 187348-17-0 (Interleukin-12); 82115-62-6 (Interferon-gamma); NIHMS356667; OID: NLM: NIHMS356667; OID: NLM: PMC3436124; 2012/03/19 [aheadofprint]; ppublish