RESUMEN
Cytokine production of unstimulated and mitogen-stimulated peripheral blood mononuclear cells of 31 children vertically infected with human immunodeficiency virus type 1 (HIV) and with different patterns of disease progression was evaluated to establish possible correlations between the immunologic and the clinical findings. Production of interferon gamma and interleukin-2 (type 1 cytokines), and of interleukin-4 and interleukin-10 (type 2 cytokines), was analyzed in seven symptom-free patients (Centers for Disease Control and Prevention class P-1B), 10 patients with mild symptoms (class P-2A), and 14 patients with severe symptoms (class P-2B-F). Cytokine production was compared with that of 10 age- and sex-matched control subjects who were seronegative for HIV. The HIV-infected patients produced significantly fewer type 1 cytokines and significantly more type 2 cytokines than the uninfected control subjects. No differences in the production of interferon gamma and interleukin-2 were detected among the different clinical categories of HIV-infected patients. In contrast, interleukin-4 production was augmented in the patients with class P-2A (p < 0.05) and class P-2B-F HIV infection (p < 0.03), in comparison with the children with class P-1B infection. The increase in interleukin-4 production was paralleled by an increase in the number of children with hyperimmunoglobulinemia E in each of the clinical groups (0% in class P-1B; 40% in class P-2A; and 71% in class P-2 B-F infection). Similarly, interleukin-10 production was increased both in patients with class P-2A and in those with class P-2B-F infection, in comparison with the children with class P-1B disease (p < 0.006 and < 0.04, respectively). These data indicate (1) that vertically acquired HIV infection results in decreased production of type 1 cytokines and in increased production of type 2 cytokines, and (2) that an increased production of type 2 cytokines correlates with hyperimmunoglobulinemia E and is present in, and may be characteristic of, the symptomatic phases of childhood HIV infection.
Asunto(s)
Citocinas/sangre , Infecciones por VIH/inmunología , VIH-1 , Inmunoglobulina E/sangre , Transmisión Vertical de Enfermedad Infecciosa , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Infecciones por VIH/transmisión , Seronegatividad para VIH/inmunología , Humanos , Inmunoglobulinas/sangre , Leucocitos Mononucleares/inmunología , Recuento de Linfocitos , Subgrupos Linfocitarios , MasculinoRESUMEN
Helper T-cell function was evaluated in 34 children infected with human immunodeficiency virus type 1, by assessing interleukin-2 production after stimulation of peripheral blood mononuclear cells with recall antigens (influenza virus, tetanus toxoid), allogeneic HLA, and phytohemagglutinin. In addition, helper T-cell function was correlated retrospectively with the incidence of opportunistic and bacterial infections. Four patterns of helper T-cell function were observed: (1) 7 (21%) of the 34 children responded to all stimuli, (2) 7 (21%) of them responded to alloantigens and phytohemagglutinin but not to recall antigens, (3) 7 (21%) responded to phytohemagglutinin but not to recall antigens or alloantigens, and (4) 13 (37%) did not respond to any of these stimuli. There were no significant differences related to different routes of acquisition among patients. Patients with functional helper T-cell defects had a history of more opportunistic (p = 0.03) and bacterial (p less than 0.001) infections than did patients with intact helper T-cell function. Thus distinct patterns of helper T-cell dysfunction exist in children infected with human immunodeficiency virus type 1 and correlate with higher frequency of infections. Comparisons of in vitro helper T-cell responses to these stimuli may be useful for detecting early functional helper T-cell defects and for monitoring progression of disease.