RESUMEN
OBJECTIVE: The present study was designed to determine whether the HLA allogeneic T helper response stimulated by semi-allogeneic cell lines could be used as an in vitro model of immune-based therapy to stimulate HIV-specific cytotoxic T lymphocytes. DESIGN AND METHODS: Semi-allogeneic cell hybrids were obtained by the fusion of peripheral blood mononuclear cells from HIV-infected patients with the allogeneic beta2-microglobulin-deficient FO1-12 melanoma cell line. These hybrids were used as antigen presenting cells for HIV envelope peptide (env)-specific cytotoxic assays. RESULTS: The hybrid cell lines express HLA class I and II antigens from both parental cells, as well as the CD86 costimulatory molecule. HIV-specific cytotoxic T lymphocyte activity was obtained when patients' peripheral blood mononuclear cells were costimulated with env peptides plus semi-allogeneic hybrids, in contrast with stimulation with either env or hybrid cells alone. Thus, the semi-allogeneic hybrids enhanced HIV-specific killing of target cells. CONCLUSIONS: Irradiated, semi-allogeneic cell hybrids engineered for individual AIDS patients provide efficient and simultaneous co-recognition of HLA allogeneic determinants and viral antigenic determinants presented by self-HLA molecules on the same antigen presenting cells and results in the generation of enhanced HIV-specific cytotoxic T lymphocyte activity.
Asunto(s)
Proteína gp120 de Envoltorio del VIH/inmunología , Proteínas gp160 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Linfocitos T Citotóxicos/inmunología , Infecciones por VIH/sangre , Humanos , Células Híbridas , Linfocitos T Citotóxicos/virología , Células Tumorales CultivadasRESUMEN
One of the proposed mechanisms for resistance to human immunodeficiency virus-1 (HIV-1) infection is the presence of antibodies against receptor for CC-chemokines (CCR5). These antibodies, detected in sera of uninfected individuals exposed to HIV, have been shown to downmodulate surface CCR5 in vivo and are able to neutralize the infectivity of CCR5 strains in vitro. To address the potential role of anti-CCR5 antibodies in HIV infection, we analyzed anti-CCR5 antibody levels in plasma from HIV-infected patients who present a wide range of CD4(+) T-cell counts and viral load. Increased levels of anti-CCR5 antibodies were found in plasma from 13/46 HIV-positive donors compared with healthy controls (0/36). However, antibody levels were not associated with disease stage evaluated by CD4(+) T-cell counts and viral load.
Asunto(s)
Seropositividad para VIH/inmunología , Inmunoglobulina G/sangre , Receptores CCR5/inmunología , Secuencia de Aminoácidos , Biomarcadores/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Seropositividad para VIH/sangre , Seropositividad para VIH/virología , Humanos , Recuento de Linfocitos , Datos de Secuencia Molecular , Pronóstico , Carga ViralRESUMEN
We have developed a comparative study of antigenic and immunogenic properties of selected immunodominant HIV-1 epitopes from p24 and gp120 proteins added to C-terminally truncated hepatitis B virus (HBV) core protein and exposed on the surface of chimeric core particles. Inserted p24 (121-210) and gp120/MN (306-328) epitopes induced the appropriate humoral and cellular immune responses against HIV-1. Superficially exposed region 160-192 of p24 also showed maximal B cell immunogenicity whereas buried region 148-162 induced maximal T cell response. Both recombinant proteins were also able to be recognized in vitro by T lymphocytes of HIV-1 asymptomatic carriers.
Asunto(s)
Vacunas contra el SIDA/inmunología , VIH-1/inmunología , Virus de la Hepatitis B , Epítopos Inmunodominantes/inmunología , Adulto , Secuencia de Aminoácidos , Animales , Femenino , Anticuerpos Anti-VIH/sangre , Proteína p24 del Núcleo del VIH/genética , Proteína p24 del Núcleo del VIH/inmunología , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , Antígenos del Núcleo de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Humanos , Epítopos Inmunodominantes/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Conejos , Proteínas Recombinantes de Fusión , Linfocitos T/inmunologíaRESUMEN
Stimulation of peripheral blood mononuclear cells (PBMC) with allogeneic PBMC (ALLO) can result in activity that inhibits the replication of human immunodeficiency virus (HIV). The present study demonstrates that strong anti-HIV activity is dependent on expression of HLA-A*02 by the responding PBMC. Anti-HIV activity was equally effective against 2 primary isolates that use different coreceptors. Neither ALLO-stimulated cell proliferation nor cytokine and beta-chemokine production was associated with the expression of HLA-A*02. ALLO-stimulated production of strong anti-HIV activity required intact PBMC and was not inhibited by monoclonal antibodies directed against nonpolymorphic regions of human leukocyte antigens (HLAs). Anti-HIV activity was generated by ALLO-stimulated CD4(+) cells, CD8(+) T lymphocytes, and monocytes from HLA-A*02-positive patients. These findings provide the first evidence that the production of an HIV inhibitory factor or factors is associated with certain HLA genes and raise new possibilities concerning the role of the major histocompatibility complex in controlling viral infections via alloantigen stimulation.