title: Negative regulation of NKG2D expression by IL-4 in memory CD8 T cells.
abstract: IL-4 is one of the main cytokines produced during Th2-inducing pathologies. This cytokine has been shown to affect a number of immune processes such as Th differentiation and innate immune responses. However, the impact of IL-4 on CD8 T cell responses remains unclear. In this study, we analyzed the effects of IL-4 on global gene expression profiles of Ag-induced memory CD8 T cells in the mouse. Gene ontology analysis of this signature revealed that IL-4 regulated most importantly genes associated with immune responses. Moreover, this IL-4 signature overlapped with the set of genes preferentially expressed by memory CD8 T cells over naive CD8 T cells. In particular, IL-4 downregulated in vitro and in vivo in a STAT6-dependent manner the memory-specific expression of NKG2D, thereby increasing the activation threshold of memory CD8 T cells. Furthermore, IL-4 impaired activation of memory cells as well as their differentiation into effector cells. This phenomenon could have an important clinical relevance as patients affected by Th2 pathologies such as parasitic infections or atopic dermatitis often suffer from viral-induced complications possibly linked to inefficient CD8 T cell responses.
authors.affiliation: Université de Lyon, Lyon F-69007, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Ventre
authors.forename: Lilia
authors.initials: L
authors.lastname: Brinza
authors.forename: Stephane
authors.initials: S
authors.lastname: Schicklin
authors.forename: Julien
authors.initials: J
authors.lastname: Mafille
authors.forename: Charles-Antoine
authors.initials: CA
authors.lastname: Coupet
authors.forename: Antoine
authors.initials: A
authors.lastname: Marçais
authors.forename: Sophia
authors.initials: S
authors.lastname: Djebali
authors.forename: Virginie
authors.initials: V
authors.lastname: Jubin
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000502:physiology
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4