title: IFN-γ regulates CD8+ memory T cell differentiation and survival in response to weak, but not strong, TCR signals.
abstract: In response to primary Ag contact, naive mouse CD8(+) T cells undergo clonal expansion and differentiate into effector T cells. After pathogen clearance, most effector T cells die, and only a small number of memory T cell precursors (TMPs) survive to form a pool of long-lived memory T cells (TMs). Although high- and low-affinity CD8(+) T cell clones are recruited into the primary response, the TM pool consists mainly of high-affinity clones. It remains unclear whether the more efficient expansion of high-affinity clones and/or cell-intrinsic processes exclude low-affinity T cells from the TM pool. In this article, we show that the lack of IFN-γR signaling in CD8(+) T cells promotes TM formation in response to weak, but not strong, TCR agonists. The IFN-γ-sensitive accumulation of TMs correlates with reduced mammalian target of rapamycin activation and the accumulation of long-lived CD62L(hi)Bcl-2(hi)Eomes(hi) TMPs. Reconstitution of mammalian target of rapamycin or IFN-γR signaling is sufficient to block this process. Hence, our data suggest that IFN-γR signaling actively blocks the formation of TMPs responding to weak TCR agonists, thereby promoting the accumulation of high-affinity T cells finally dominating the TM pool.
authors.affiliation: Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Institute of Immunology, Charité Berlin, 12200 Berlin, Germany;
authors.forename: Diana
authors.initials: D
authors.lastname: Stoycheva
authors.affiliation: Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Institute of Immunology, Charité Berlin, 12200 Berlin, Germany;
authors.forename: Katrin
authors.initials: K
authors.lastname: Deiser
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany;
authors.forename: Lilian
authors.initials: L
authors.lastname: Stärck
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Organ-Specific Immune Regulation, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; and.
authors.forename: Gopala
authors.initials: G
authors.lastname: Nishanth
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Organ-Specific Immune Regulation, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; and.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schlüter
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany; Institute of Biology, Humboldt University Berlin, 10115 Berlin, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Uckert
authors.affiliation: Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Institute of Immunology, Charité Berlin, 12200 Berlin, Germany; thomas.schueler@med.ovgu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schüler
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D019041:L-Selectin / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D019041:L-Selectin; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D020825:T-Box Domain Proteins; D058570:TOR Serine-Threonine Kinases; D000096743:Interferon gamma Receptor; C491198:Eomes protein, mouse; C052617:Bcl2 protein, mouse; C546843:mTOR protein, mouse