Avian erythroblastosis virus induced accessory cell dysfunction and RRR-alpha-tocopheryl succinate effects on IL-1 and IL-2 production

Avian erythroblastosis virus (AEV) is an acute replication-defective retrovirus that causes severe immunosuppression and a fatal erythroblastic leukemia in susceptible chickens. In the present studies, macrophage accessory cell and splenic T cell dysfunctions were characterized in AEV infected chickens. Macrophages from AEV infected chickens failed to supply the necessary accessory functions required for normal T cell activity. Although macrophages from normal chickens could restore suppressed T cell blastogenic responses of splenic lymphocytes from AEV immunosuppressed chickens during the early stages of infection, by 12 days post infection, they were without effect suggesting that suppressed responses were due to both macrophage and T cell dysfunctions. The addition of T cell growth factor (IL-2)(produced in the presence of vitamin E succinate) to splenic lymphocyte cultures from chickens 6 day after infection and to co-cultures at this stage of infection resulted in amelioration of AEV induced immune suppression. Thymic atrophy with accompanying depletion of thymic lymphocytes but near normal levels of T helper: T suppressor cells were observed at 6 and 12 days post AEV infection. Splenic enlargement was also observed. Decreased numbers of CD8{dollar}sp+{dollar} cells were found among splenic lymphocytes from 12 day post AEV infected chickens. The effects of vitamin E succinate on IL-2 production in the avian model system examined was determined to be similar to effects produced by other antioxidants. Using a murine T cell line, vitamin E succinate was demonstrated to enhance IL-2 production. In the murine model system, vitamin E succinate was demonstrated to synergize with the phorbol ester (PMA) to enhance IL-2 production/release. Enhanced IL-2 production in the murine system was not due to an antioxidant effect. The optimal concentration of vitamin E succinate that induced maximum levels of IL-2 production was the same in both model systems examined. These studies also investigated the effects of vitamin E succinate on IL-1 production by a murine macrophage cell line. Vitamin E succinate was found to enhance IL-1 secretion. Synergism between vitamin E succinate and PMA was also observed in these studies.