Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa)

Blood. 2012 Feb 9;119(6):1418-27. doi: 10.1182/blood-2011-06-363655. Epub 2011 Dec 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • Cell Line
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Flow Cytometry
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunocompetence / immunology
  • Immunocompromised Host / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / immunology
  • Polymerase Chain Reaction
  • Protein Binding
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, IgG / immunology*
  • Receptors, IgG / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Virus Replication / genetics
  • Virus Replication / immunology

Substances

  • Immunoglobulin G
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, IgG
  • Interferon-gamma