The proposed studies will be conducted on specimens already collected from HIV infected mothers and their offspring, as well as on samples that will be available, from ongoing prospective studies of HIV + pregnant women. Factors to be evaluated in the pregnant women will include: (1) functional antibodies which neutralize homologous strains of virus or mediate ADCC, antibodies reactive to envelope synthesis of antibodies to the envelope antigens by peripheral blood B cells; and c) cytotoxic T cells and precursors. The transfer of these antibodies to their infant will be examined in selected maternal/infant pairs. Since ADCC is likely to be a major specific mechanism in the fetus/neonate to eliminate infected cells during the early stage, the ability of cord blood lymphocytes, monocytes and polymorphonuclear cells to mediate this function will be ascertained. Differences in neonatal immune cells likely to be targets of infection, including monocytes, and memory and naive CD4 + lymphocytes, will be studied for susceptibility to HIV infection, latency and replication, with both vertically-transmitted and non-transmitted virus strains. The recent findings of variations in the number of memory/naive T-cells and of activated mononuclear cells in HIV infected infants >2 months of age also indicate the need of quantitative analysis of such cells in at-risk babies early after birth. Results of these immunological studies will be examined in relation to data collected from clinico-epidemiological, virological and early diagnostic studies being conducted in the same cohort. Analyses of possible correlation to maternal-infant transmission or nontransmission of HIV should help to identify critical immune factors and to assist in defining the timing of transmission.
