title: TCR-dependent sensitization of human γδ T cells to non-myeloid IL-18 in cytomegalovirus and tumor stress surveillance.
abstract: Human γδ T cells contribute to tissue homeostasis under normal conditions and participate in lymphoid stress surveillance against infection and tumors. However, the molecular mechanisms underlying the recognition of complex cell stress signatures by γδ T cells are still unclear. Tumor cells and human cytomegalovirus (HCMV)-infected cells are known targets of γδ T cells. We show here that many tumor and CMV-infected cells express caspase-1 inflammasomes and release interleukin (IL)-18. Engagement of the T-cell receptor (TCR) on Vδ2negγδ T cells controlled the direct innate immune sensing of IL-18 that enhanced cytotoxicity and interferon gamma (IFNγ) production. This TCR-dependent sensitization to IL-18 was mediated by the upregulation of the innate IL-18 receptor β chain (IL-18Rβ) expression. These findings shed light on inflammasomes as a unified stress signal of tumor and infected cells to alert γδ T cells. Moreover, uncovering the TCR-mediated sensitization of γδ T cells to inflammatory mediators establishes a molecular link between the innate and adaptive immune functions of γδ T cells that could fine tune the commitment of antigen-experienced γδ T cells to inflammatory responses.
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France ; Nephrology and Renal Transplantation Department; Bordeaux University Hospital ; Bordeaux, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Guerville
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Daburon
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Marlin
authors.affiliation: INSERM U916 VINCO , Institut Bergonié , Bordeaux, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Lartigue
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France.
authors.forename: Severine
authors.initials: S
authors.lastname: Loizon
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pitard
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France ; Nephrology and Renal Transplantation Department; Bordeaux University Hospital ; Bordeaux, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France ; Immunology and Immunogenetics Laboratory, Bordeaux University Hospital , Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
authors.affiliation: Bordeaux University; CIRID ; Bordeaux, France ; CNRS , UMR 5164 , Bordeaux, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Faustin
keywords: IL-18; TCR; cancer; caspase-1; cytomegalovirus; immunology; inflammasome; γδ T cells