title: Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa).
abstract: Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality in transplant recipients. Long-term protective immunity against HCMV requires both sustained specific T-cell response and neutralizing IgG production, but the interplay between these effector arms remains poorly defined. We previously demonstrated that γδ T cells play a substantial role as anti-HCMV T-cell effectors. The observation that CD16 (FcγRIIIA) was specifically expressed by the majority of HCMV-induced γδ T cells prompted us to investigate their cooperation with anti-HCMV IgG. We found that CD16 could stimulate γδ T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. Although CD16(+)γδ T cells did not mediate ADCC against HCMV-infected cells, in accordance with the low level of anti-HCMV IgGs recognizing infected cells, they produced IFNγ when incubated with IgG-opsonized virions. This CD16-induced IFNγ production was greatly enhanced by IL12 and IFNα, 2 cytokines produced during HCMV infection, and conferred to γδ T cells the ability to inhibit HCMV multiplication in vitro. Taken together, these data identify a new antiviral function for γδ T cells through cooperation with anti-HCMV IgG that could contribute to surveillance of HCMV reactivation in transplant recipients.
authors.affiliation: Université de Bordeaux, Bordeaux, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.forename: Vincent
authors.initials: V
authors.lastname: Pitard
authors.forename: Xavier
authors.initials: X
authors.lastname: Sicard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Garrigue
authors.forename: Omar
authors.initials: O
authors.lastname: Hawchar
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG; D007371:Interferon-gamma