VITAMIN-E-DEFICIENCY AND IMMUNE DYSFUNCTION IN RETROVIRUS-INFECTED C57BL 6 MICE ARE PREVENTED BY T-CELL RECEPTOR PEPTIDE TREATMENT/

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing muri ne acquired immunodeficiency syndrome (AIDS), which is functionally si milar to human AIDS. Retrovirus infection inhibited release of T-helpe r 1 cytokines, stimulated secretion of T-helper 2 cytokines and induce d hepatic and cardiac vitamin E deficiency with increased lipid peroxi des. We hypothesized that the immune dysfunction caused increased oxid ation and loss of vitamin E. Because T-cell receptor (TCR) peptide tre atment blocked the excessive stimulation of a T-cell subset by retrovi ral superantigens, we tested whether maintenance of normal immune func tion during infection prevented excessive oxidative damage. The TCR pe ptide treatments with doses > 100 mu g/mouse and administered 2-4 wk p ostinfection significantly inhibited the retrovirus-induced immune dys function, concomitantly reduced tissue oxidative damage and thereby la rgely maintained vitamin E concentration in the liver and heart. Reduc ing the dose of peptide or delaying administration until early murine AIDS had developed resulted in severe immune dysfunction that caused e levated tissue lipid peroxidation and loss of vitamin E. The TCR pepti de treatment partially maintained production of interleukin-2 (IL-2) a nd prevented retrovirus-induced elevated production of IL-6 by splenoc ytes in vitro. In conclusion, TCR peptide treatment during murine retr ovirus infection ameliorated immune dysfunction and thus prevented inc reases in tissue lipid peroxidation and vitamin floss. T-cell immune d ysfunction and its prevention by TCR peptide treatment is important in the therapy of vitamin E deficiency induced by retrovirus infection.