IMMUNOLOGICAL CHARACTERIZATION OF CHILDREN VERTICALLY INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS, WITH SLOW OR RAPID DISEASE PROGRESSION

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 dis ease progression was evaluated to establish possible correlations betw een the immunologic and the clinical findings, Production of interfero n 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-PB-F), Cytokine production was compared with that of 10 age- and sex-matched control subjects who were seronegative for HI V. The HIV-infected patients produced significantly fewer type 1 cytok ines and significantly more type 2 cytokines than the uninfected contr ol 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 augm ented in the patients with class P-2A (p <0.05) and class P-SB-F HIV i nfection (p <0.03), in comparison with the children with class P-1B in fection, 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 dis ease (p <0.006 and <0.04, respectively), These data indicate (1) that vertically acquired HIV infection results in decreased production of t ype 1 cytokines and in increased production of type 2 cytokines, and ( 2) that an increased production of type 2 cytokines correlates with hy perimmuno-globulinemia E and is present in, and may be characteristic of, the symptomatic phases of childhood HIV infection.