title: Expression Profile of Human Fc Receptors in Mucosal Tissue: Implications for Antibody-Dependent Cellular Effector Functions Targeting HIV-1 Transmission.
abstract: The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection. However, the ability of antibody-dependent cellular effector mechanisms to impact on early mucosal transmission events will depend on a variety of parameters including effector cell type, frequency, the class of Fc-Receptor (FcR) expressed, the number of FcR per cell and the glycoslyation pattern of the induced antibodies. In this study, we characterize and compare the frequency and phenotype of IgG (CD16 [FcγRIII], CD32 [FcγRII] and CD64 [FcγRI]) and IgA (CD89 [FcαR]) receptor expression on effector cells within male and female genital mucosal tissue, colorectal tissue and red blood cell-lysed whole blood. The frequency of FcR expression on CD14+ monocytic cells, myeloid dendritic cells and natural killer cells were similar across the three mucosal tissue compartments, but significantly lower when compared to the FcR expression profile of effector cells isolated from whole blood, with many cells negative for all FcRs. Of the three tissues tested, penile tissue had the highest percentage of FcR positive effector cells. Immunofluorescent staining was used to determine the location of CD14+, CD11c+ and CD56+ cells within the three mucosal tissues. We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria. The potential implication of the observed FcR expression patterns on the effectiveness of FcR-dependent cellular effector functions to impact on the initial events in mucosal transmission and dissemination warrants further mechanistic studies.
authors.affiliation: Imperial College London, Department of Medicine, Section of Virology, Group of Mucosal Infection and Immunity, London, United Kingdom.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Cheeseman
authors.affiliation: Northwestern University, Feinberg School of Medicine, Cell and Molecular Biology Department, Chicago, Illinois, United States of America.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Carias
authors.affiliation: Imperial College London, Department of Medicine, Section of Virology, Group of Mucosal Infection and Immunity, London, United Kingdom.
authors.forename: Abbey B
authors.initials: AB
authors.lastname: Evans
authors.affiliation: Imperial College London, Department of Medicine, Section of Virology, Group of Mucosal Infection and Immunity, London, United Kingdom.
authors.forename: Natalia J
authors.initials: NJ
authors.lastname: Olejniczak
authors.affiliation: Imperial College London, Department of Surgery, St. Mary's Hospital, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Ziprin
authors.affiliation: Imperial College London, Department of Medicine, Section of Virology, Group of Mucosal Infection and Immunity, London, United Kingdom.
authors.forename: Deborah F L
authors.initials: DF
authors.lastname: King
authors.affiliation: Northwestern University, Feinberg School of Medicine, Cell and Molecular Biology Department, Chicago, Illinois, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
authors.affiliation: Imperial College London, Department of Medicine, Section of Virology, Group of Mucosal Infection and Immunity, London, United Kingdom.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001773:Blood Cells / Q000166:cytology / Q000276:immunology; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D020869:Gene Expression Profiling; D005836:Genitalia, Female / Q000166:cytology / Q000276:immunology*; D005837:Genitalia, Male / Q000166:cytology / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D009928:Organ Specificity; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D012007:Rectum / Q000166:cytology / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015703:Antigens, CD; C428200:FCGR3B protein, human; C036832:Fc(alpha) receptor; D058851:GPI-Linked Proteins; D015483:HIV Antibodies; D011961:Receptors, Fc; D017452:Receptors, IgG