title: CD8(+) T cells sabotage their own memory potential through IFN-γ-dependent modification of the IL-12/IL-15 receptor α 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-γ-dependent modification of the IL-12/IL-15Rα 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.
authors.affiliation: Department of Surgery, Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Kohlhapp
authors.forename: Andrew
authors.initials: A
authors.lastname: Zloza
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: O'Sullivan
authors.forename: Tamson V
authors.initials: TV
authors.lastname: Moore
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lacek
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jagoda
authors.forename: James
authors.initials: J
authors.lastname: McCracken
authors.forename: David J
authors.initials: DJ
authors.lastname: Cole
authors.forename: José A
authors.initials: JA
authors.lastname: Guevara-Patiño
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000276:immunology*; D053647:Receptors, Interleukin-15 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D019409:Interleukin-15; D053707:Receptors, Interleukin-12; D053647:Receptors, Interleukin-15; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma