RESUMEN
Langerhans cells (LC) are bone marrow-derived, Ia+, CD1+, CD4+, ATPase+ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV-seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17+ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as well as cytopathic changes in approximately one-third of the LC population were demonstrated by electron microscopy. These results strongly suggest that LC may harbor HTLV-III/LAV. The infection of LC with this retrovirus may have deleterious consequences for the immunologic functions of this cell system and may thus contribute to both the acquisition of immunodeficiency and the infectious and neoplastic complications of AIDS.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/microbiología , Epidermis/microbiología , VIH/aislamiento & purificación , Células de Langerhans/microbiología , Síndrome de Inmunodeficiencia Adquirida/patología , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Antígenos de Diferenciación de Linfocitos T , Antígenos de Superficie/análisis , Efecto Citopatogénico Viral , Epidermis/patología , Anticuerpos Anti-VIH , Humanos , Células de Langerhans/análisisRESUMEN
Intra-blood-brain-barrier production of virus-specific antibody is good evidence of infection within the blood-brain barrier. Patients with the acquired immuno-deficiency syndrome (AIDS) have an increased incidence of neurologic abnormalities--i.e., unexplained, diffuse encephalopathy manifested clinically as chronic progressive dementia. To define the role of human T-cell lymphotropic virus Type III (HTLV-III), the etiologic agent of AIDS, in the pathogenesis of neurologic dysfunction, we compared cerebrospinal fluid and serum from patients with neurologic symptoms associated with AIDS and the AIDS-related complex for the presence of antibodies directed against HTLV-III. Antibodies directed against HTLV-III antigens were detected by four immunologic tests: a fixed-cell immunofluorescence assay, an enzyme-linked immunosorbent assay, immunoblots of viral lysates, and immunoprecipitation of cellular lysates. All patients were seropositive, and 22 of 23 (96 per cent) had HTLV-III-specific antibodies in their cerebrospinal fluid. Unique oligoclonal IgG bands were detected in the cerebrospinal fluid, and the rate of IgG synthesis within the blood-brain barrier was elevated. In eight of nine patients tested, the enzyme-linked immunosorbent assay showed that the percentage of HTLV-III-specific IgG in cerebrospinal fluid was higher than in serum, suggesting that HTLV-III infection of neurologic tissue occurs in the majority of patients with neurologic disease associated with AIDS or its related complex.
Asunto(s)
Barrera Hematoencefálica , Deltaretrovirus/inmunología , Inmunoglobulina G/biosíntesis , Enfermedades del Sistema Nervioso/inmunología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adulto , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/líquido cefalorraquídeo , Encefalopatías/etiología , Preescolar , Demencia/etiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Pruebas de PrecipitinaRESUMEN
A high correlation was found among antibodies to human T-cell leukemia virus type III (HTLV-III), acquired immunodeficiency syndrome, and acquired immunodeficiency syndrome-related complex. With the Western blot technique the antigens (shown as proteins with molecular weights given in thousands) in HTLV-III lysates recognized by positive sera have been identified as p120, p66, p51, p41, p31, p24, and p17. The most common reactivity was toward p41. Lectin fractionation identified p120 and p41 as glycoproteins. Studies using mouse monoclonal antibodies to the p24 proteins of HTLV-I, -II, and -III showed that HTLV-I and -II have common epitopes in p24 molecule, but these are not the cross-reactive epitopes present on HTLV-III p24.