Phagocytic cells (monocyte/macrophages and polymorphonuclear cells (PMNs) play a key role in the immune response of normal and sick infants. Both types of cells are widely distributed in blood, bone marrow, tissues (e.g. liver and spleen), placental tissue and breast milk. Phagocytic cell function not only plays a key role in bacteria defenses, but also a yet not well defined role in infection, intrauterine or postnatal malnutrition, hypogycemia, anoxia, etc.) results in diminished extrinsic viral resistance (EVR), enhanced viral replication, diminished monocyte and PMN-mediated cytotoxicity, and altered monocytic regulatory function. Alteration of anti-viral defenses of phagocytic cells, and their correlation with cytotoxicity and phenotype in response to immaturity, infection and malnutrition will be undertaken. EVR is measured by a quantitative plaque reduction assay utilizing herpes simplex virus type I in Vero cells as well as assays of viral release into supernatants from infected CEM cell supernatants. Preliminary studies indicate subtle defects in newborn EVR involving both mononuclear and monocytic cells. A major goal is to extend these studies to PMNs, inasmuch as this cell may have major anti-viral properties, particularly antibody-dependent cellular cytotoxicity (ADCC) and EVR. Defects in EVR are correlated with cell phenotype, activation and cytotoxic capacity. Flow cytometry is done to assess Fc and complement receptors and DR expression; chemiluminescence, quin-2 and phallacadin assays are used to assess activation. Cytotoxic assays utilize HSV- infected Raji or CEM cell lines; both spontaneous and ADCC are utilized and correlated with EVR. Modulation of EVR by virus infections, lymphokines, heteroantibodies and immunoglobulin will be done to search for pharmacologic methods to enhance anti-viral defenses. These studies define defects and mechanisms of newborn anti-viral defenses, identify immunologic defects in viral-infected infants, and suggest new therapeutic strategies. These studies are also relevant to anti-viral strategies in perinatal HIV infections.
