Gamma IFN is produced by human mononuclear cells in culture from seropositive donors in response to cytomegalovirus (CMV), herpes simplex virus, mumps virus, and varicella zoster virus (VZV) antigens. The recent availability of an RIA for gamma IFN (IMRX™, Centocor Inc., Malvern, PA) makes gamma IFN production a potentially more rapid and sensitive measure of cell-mediated immunity than a six day blastogenesis assay. Mononuclear cells were obtained from 32 healthy adults (18 CMV seropositive (S+) and 14 CMV seronegative (S−)) by Ficoll hypaque gradients and cultured in triplicate in microtiter plates containing either CMV, VZV, tetanus antigen or phytohemagglutinin (PHA). Lymphocyte blastogenesis (3H thymidine uptake) and gamma IFN were determined on day 6. The mean stimulation index (SI) of S+ (10.01 ± 9.46) was significantly greater than S− individuals (1.04 ± 0.67) (p< 0.001). Similarly, the gamma IFN stimulation index, defined as the concentration of gamma IFN (NIH units/ml) induced by viral antigen divided by the concentration induced by control antigen, was 93.82 ± 111.45 for (S+) and 2.49 ± 2.25 for (S-) (p< 0.005). Significant increases in gamma IFN also occurred with VZV and tetanus antigens. In 3 (S+) and 3 (S−) individuals, gamma IFN was assayed daily. Significant levels of gamma IFN (> 10 NIH units/ml) were observed for S+ individuals at 24 hours with peak levels at 4 days. No detectable levels of IFN (< 2 NIH units/ml) were observed in (S−) individuals during the six day incubation. In conclusion, mononuclear cell production of gamma IFN in a sensitive assay for CMI and is readily detectable in vitro as early as 24 hours.
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D'Andrea, A., Plotkin, S., Douglas, S. et al. 968 IMMUNE-SPECIFIC GAMMA INTERFERON (IFN) PRODUCTION CORRELATES WITH LYMPHOCYTE BLASTOGENESIS. Pediatr Res 19, 272 (1985) doi:10.1203/00006450-198504000-00998