971 Impaired Production of Immune (Pha-Induced) Interferon in Newborns Is Due to a Functionally Immature Acrophage

Abstract

Human foreskin fibroblasts acutely infected with VZV were exposed to VZV antibody-posi.tive human serum and human mononuclear cells (MC) in a 6-hr 5 1~r release assay. Specific lysis could be detected by 60 min and was proportional to the effector cel1:target cell ratio. The reaction was temperature dependent, proceeding optimally at 37OC. Only VZV antibody-positive serum mediated the reaction, and uninfected targets were not lysed. MC alone had little or no lytic activity. Median antibody titers of 1000 were noted in the serum of normal adults without a history of zoster. The antibody was of the IgG class as indicated by its adsorption with S. aureus containing protein A, its presence in high titer in inunune serum globulin and zoster immune globulin, and its quantitative placental transfer. A requirement for effector cell IgG-Fc receptors was shown by blocking of ADCC by protein A and inhibition of effector cell activity by heat-aggregated gamma globulin. Lymphocytes were more effective as killer cells than were monocytes or polyorphonuclear leukocytes. ADCC was able to lyse cells earlier in the VZV infectious cycle than antibody-dependent complement-mediated lysis. These results are the first demonstration of ADCC against VZV-infected cells and suggest a mechanism whereby IgG antibody aids in prophylaxis of infection or reduces the severity of exogenous reinfection. I n the newborn, serum l e v e l s o f a l l 4 o f these proteins are normally reduced. Despite t h i s physiologic hypocomplementemia, umbilical cord blood shows a much higher r a t i o o f these components w i t h nearly 70% (n=200) o f neonates being greater than 1.3. These data suggest t h a t the a c t i v i t y o f B1H and C3bINA i n regulating the i n t e r a c t i o n o f C3 and f a c t o r B i s more potent i n the newborn. Measurement o f s p e c i f i c functional B1H a c t i v i t y revealed l i t t l e difference between the a d u l t and newborn i n the number o f B1H molecules required t o i n a c t i v a t e 1 e f f e c t i v e C3b molecule. By contrast, s p e c i f i c C3bINA functional assays demons t r a t e t h a t the newborn requires 50-75% fewer C3bINA molecules than the a d u l t i n order t o i n a c t i v a t e 1 e f f e c t i v e C3b molecule. Thus, the neonate appears t o have an a l t e r e d form o f C3bINA which i s 2-3 times more potent than i t s a d u l t counterpart. This a l t e r e d molecule could allow f o r less C3b deposition on an offending agent and, therefore, less e f f i c i e n t opsonization. The effect of inadequate dietar; iron uptake on cellular immune responses was studied in weanling female mice C57BLl6, which were fed either control (C), iron deficient (DEF) or pairfed (PF) C diets. The DEF mice showed a significant decrease in the delayed cutaneous hypersensitivity feaction to dinitroflurobenzene D FB) as measured by the inflammatory skin response (p<.001) and f2yI-dUR incorporation into sensitized ears (p<.001). When a sinfle dose of imferon was given to DEF mice prior to recall, the 251-~UR...

Intracellular cytokine production and cytokine receptor interaction of cord mononuclear cells: relevance to cord blood transplantation

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