The rate of mother to infant transmission of HIV infection is reported to be between 12-30%. The various factors influencing vertical transmission and progression of disease in the infected infant are still largely unknown, but it is likely that a major factor is the functional capacity of the immune system in the mother and infant. Studies of the immune system have mostly focused on humoral immunity. This application will focus on understanding cellular immune responses and applications to early diagnosis of infants. CD4 cell concentration is a useful clinical determination but may not correlate with CD4 functional capacity. Therefore, the first specific aim will be to evaluate CD4 functional activity and correlate it with the number of infected CD4 cells by a flow cytometric technique and in situ PCR. These assays will aid in determining if T helper responses in mothers are protective against HIV transmission to the fetus. Also, the T helper responses of the neonate to HIV peptides as well as the other CD4 assays may prove to be useful markers of infection in the neonate. The second specific aim is to evaluate the role of CD8+ cells in modulating HIV responses. CD8 cells have been shown to have antiretroviral activity. They will assess the role and mechanisms of CD8 antiretroviral activity in preventing HIV transmission to the infant and modifying the effect of HIV infection in the mother and infant.
The third aim will be to characterize lymphocyte subsets during fetal development and determine the susceptability of fetal cells to HIV infection. Evaluating HIV infectability of fetal cells obtained from normal individuals early in gestation will give insights into the mechanism of fetal acquisition and the timing of HIV infection. The major source of patients for this study will be from the University of Illinois Women and Infants Transmission Study (WITS) while the control pregnant women will be from the UI prenatal clinics. A population of uninfected patients undergoing fetal blood sampling for prenatal diagnosis from Prentice Womens Hospital, Northwestern University will be used. It is expected that 100 HIV antibody positive mother/infant pairs and 100 negative pairs will be enrolled over the next 30 months and up to 60 fetal samples obtained. This study will help expand our understanding of the role of specific lymphocyte populations in preventing transmission of HIV from mother to fetus and will increase our ability to diagnose infection in the infant at an early age.
