In 50% of children congenitally infected with human immunodeficiency virus (HIV), the diagnosis was made during the first year of life, and in 82% by 3 years of age. Although the disease course is variable, and long asymptomatic periods are sometimes present, in general the course is ultimately characterized by progressive immune dysfunction. An HIV infection, through its effect on CD4+ helper T lymphocytes, can result in profound defect in cell-mediated immunity. Although many of the manifestations of HIV infection in children are similar to those in adults, some are different, and they might reflect the subtle differences in the immune repertoire of infants. We propose to analyze the functional abnormalities of lymphocytes in infants from 40 HIV-infected mothers in three specific areas: (1) We will evaluate quantitative and qualitative changes among different subsets of peripheral blood mononuclear cells (PBMC): monocytes, T cells, B cells and natural killer (NK) cells in infants at 1 day, 2 weeks, 2, 4, 6, 12, 18, 21, 24, 30, 36, 42, 48 and 54 months of age by two-color indirect immunofluorescence with specific monoclonal antibodies (mABs). Infants from 20 non-infected but substance- abuse mothers and 20 healthy mothers will serve as control. (2) Using radioimmunoassay (RIA) and/or reverse-transcription polymerase chain reaction (RT-PCR) technique we will evaluate pattern of lymphokine/cytokine production by monocytes, T cells and NK cells at time 0, 6, and 12 hr after stimulation with phorbol esters and calcium ionophore, or immobilized anti- CD3 antibody. An increased number of T lymphocytes expressing a novel T cell receptor (TCR) -gammadelta has been demonstrated in humans during bacterial infection, and in HIV-infected T cell cultures in vitro. Because one common manifestation of HIV-infection in children is recurrence of serious bacterial infection, we will analyze population of gamma+delta+ T cells in all infants using anti-TCR-gammadelta mAbs. If an increased number of gamma+delta+ T cells correlates with the clinical deterioration, these cells will be expanded in culture and analyzed for their inherent cytotoxic activities, and for lymphokine production.
