An assay system is described which allows simultaneous measurement of antiviral (AV) and antiproliferative (AP) activities of various interferons (IFNs) with the same indicator cells and tests one biological function, i.e. the reduction of DNA synthesis. Human IFN-alpha, -beta, and -gamma preparations were investigated for their respective AV and AP activities. In repeated independent experiments the AP:AV ratio was found to be constant for each IFN preparation. However, striking difference in the AP:AV ratios was found between the preparations, being highest in IFN-gamma and lowest in IFN-alpha. The validity of this assay was substantiated by the observation that the AP activity of the IFNs is not influenced by virus once the cells are protected by sufficient amounts of IFN and that the score of the microscopically assessed cytopathic effect (CPE) strongly correlates with the reduction of [3H]TdR uptake in the cultures. The AP:AV ratio of a Corynebacterium parvum induced IFN resembled that of the IFN-alpha-reference, suggesting that contrary to previous reports, the C. parvum induced is of alpha type. It is suggested that the assay system presented here provides a simple means not only of comparing AP and AV ratios of various IFNs but also of characterizing IFNs of unknown type.
An assay system is described which allows simultaneous measurement of antiviral (AV) and antiproliferative (AP) activities of various interferons (IFNs) with the same indicator cells and tests one biological function, i.e. the reduction of DNA synthesis.
The correlation between phytohemagglutin in (PHA) induced blast cell transformation (BCT) and production of lymphotoxin (LT), a cytotoxic mediator of cellular immunity, was studied in the cord blood lymphocytes of 17 normal newborns. Twelve normal adults served as controls. BCT was estimated as uptake of 3-H-thymidine, and LT as the percent inhibition of DNA synthesis of growing target cells. BCT by newborn lymphocytes was slightly greater than that of adults. By contrast, LT production by the newborns was only 40 that of the adults. Calculation of an “LT Index” (ratio of LT production to BCT) revealed that for any degree of BCT, newborn lymphocytes produced only one-fourth as much LT as did adult cells. In 6 infants, the percent of lymphocytes forming rosettes with sheep red cells (T-cell rosettes) averaged 80% (range 63-90%), which is comparable to that of adults. The combination of impaired mediator production with normal BCT represents a dissociation of lymphocyte function which appears to be a stage in the normal maturation of cellular immune competence. This may, in part, explain the undue susceptibility of newborn infants to certain mycobacterial, fungal and viral infections.