This is a 4 year competitive renewal which proposes to identify immunologic factors that influence the pathogenesis of HIV disease during pregnancy and are associated with vertical transmission of HIV infection. The hypotheses to be tested are three fold. The first is that immunologic alterations of pregnancy that shift toward T2 cytokines and immune activation result in up regulation of HIV replication and down-regulation of the cellular immune response; the second is that compromise of the placenta by up-regulation of cytokines and adhesion molecules facilitates placental transfer of HIV and activation of the neonatal immune system; and the third is that deficient neonatal cellular immune mediation of resistance to and control of HIV infection is related to neonatal HIV infection. They will prospectively study HIV pregnant women and assess CD8 lymphocyte cytotoxicity and antiviral suppression, characterize cytokine profiles, surface phenotype of maternal peripheral T-cells and t cell clones and relate these to each other, to viral load, and to HIV transmission to infants. They will perform immunohistochemical evaluation of placentas from HIV infected pregnancies; for cytokine profiles in the trophoblast, villous stroma, and decidua; for expression of integrins and selectins that are important in cell interactions and; for HIV tropism and the presence of other infectious agents that could alter the cytokine balance, activate the maternal and fetal immune systems and facilitate passage of HIV. Placental alterations will be related to neonatal immunologic activation and HIV transmission. They will study infants of HIV infected mothers that are <6 months old and characterize T-cell phenotype and function of cytotoxic CD8 cells, assess the function of CD8 cells in inhibiting replication of autologous or maternal HIV isolates. CD8 cell function and phenotype will be related to each other and to viral load and infection status of the infant.
| Ahmed, Simi T; Darnell Jr, James E (2009) Serpin B3/B4, activated by STAT3, promote survival of squamous carcinoma cells. Biochem Biophys Res Commun 378:821-5 |
