Local Synthesis of IgG Antibodies to HIV within the Female and Male Genital Tracts during Asymptomatic and Pre-AIDS Stages of HIV Infection

Abstract

Paired sera and cervicovaginal secretions or seminal fluids, obtained from HIV-1-infected, clinically asymptomatic women (n = 41) and men (n = 12), were investigated in order to test the hypothesis of a local synthesis of IgG to HIV in the female and male reproductive tracts. Anti-gp41 + p24 IgG was evaluated by an IgG immunocapture assay, and anti-gp160 IgG by an indirect ELISA. Estimation of anti-HIV IgG-specific activities was carried out after ponderal determination of total IgG and evaluation of anti-HIV IgG activity. IgG to gp41 + p24, as well as IgG to gp160, were specifically detected in all sera, cervicovaginal secretions, and seminal fluid samples from all tested HIV-1-infected subjects. The mean specific activities of IgG to gp41 + p24 in cervicovaginal secretions and in seminal fluids were about 33-fold (in women) and 16-fold (in men) that of the corresponding sera; similarly, the mean specific activities of IgG to gp160 in genital secretions were about 17-fold (in women) and 10-fold (in men) that of the corresponding sera. IgGs to HIV are constantly detected in genital secretions from HIV-1-infected subjects, and appear to be largely synthesized in situ within the genital tract of both genders.

Sperm Characteristics and Accessory Sex Gland Functions in Hiv-Infected Men

“…The high prevalence of leucocytospermia in HIV-1 patients indicates the possibility that increased transudation of serum antibodies into semen occurs in men with genital tract inflammation. White blood cells in semen not only provide a vehicle for the presence of HIV-1, they may also play a role in the sexual transmission of HIV-1 [5]. The present study further supports the proposition that genital tract inflammation as a cofactor affects HIV-1 titers in semen and its sexual transmission [3,17].…”

“…During this acute phase of the infection, B cells produce antibodies that neutralize the virus, and activated killer T cells multiply and destroy the virus, so by the time the antibodies are found in blood, the infection is generally permanent [4]. More than 90% of people with AIDS develop circulating immune complexes (CICs) and lymphocytotoxic antibodies (LTCAs) and those HIV-infected people who do not develop CICs or LTCAs do not progress to AIDS [5]. It is suggested that exposure of seminal lymphocytes to infectious agents precipitates the production of antibodies to the virus [5].…”

“…More than 90% of people with AIDS develop circulating immune complexes (CICs) and lymphocytotoxic antibodies (LTCAs) and those HIV-infected people who do not develop CICs or LTCAs do not progress to AIDS [5]. It is suggested that exposure of seminal lymphocytes to infectious agents precipitates the production of antibodies to the virus [5].…”

Antiviral Antibodies and T Cells Are Present in the Foreskin of Simian Immunodeficiency Virus-Infected Rhesus Macaques

“…HIV-specific CD8 ϩ T cells are present in semen and pre-ejaculate fluids (18,33), and SIV-specific CD8 ϩ T cells have been found in semen of infected rhesus macaques (RMs) (20). Furthermore, HIV-specific antibodies are present in seminal plasma (5,28,35). However, no information exists regarding HIV-specific immunity in the foreskin or glans of the penis.…”

Molecular characterization of the cervical and systemic B-cell repertoire

“…50,54,61,62 In this regard, the observed mucosal compartmentalization adds credence to the presence of HIV-1 specific IgG and IgA in cervicovaginal secretions that is absent from the serum in some HEPS individuals. 63,69 The frequency of somatic hypermutation among the V H genes of isotype switched systemic and mucosal B cells is distinct. The B cells of the cervical compartment are oligoclonal with V H genes containing more somatic mutations than those found in the peripheral blood.…”