Prevention of immunodysfunction, tissue vitamin E deficiency, and excessive lipid peroxidation by vitamin E supplementation and T cell receptor peptide treatment during murine AIDS

Abstract

LP-BM5 murine leukemia retrovirus infection in C57BL/6 mice rapidly induces murine AIDS with many functional similarities to human AIDS, including progressive lymphoproliferation and severe immunodeficiency. The present studies indicate that retrovirus infection induces immune dysfunctions mostly via modulating T and B cell proliferation, natural killer cell toxicity, and cytokine secretion. In addition, retrovirus infection causes oxidative damage via nuclear factor κB (NF-κB) activation, excessive free radicals production, and antioxidant deficiency. Such oxidative damage has the theoretical potential to accelerate the development of AIDS via immunosuppression secondary to antioxidant deficiency. Synthesized T cell receptor (TCR) peptides treatment largely blocks the excessive stimulation of a T cell subset by retroviral superantigens, normalizes the retrovirus-induced aberrant cytokines production, thereby significantly ameliorates immune dysfunction, and prevents excessive lipid peroxidation and antioxidant deficiency in murine AIDS. Results from the current studies suggest that dietary vitamin E supplementation significantly prevents the dysregulation of cytokines production, excessive tissue lipid peroxidation, and vitamin E deficiency. Furthermore, vitamin E may play an important role in inhibiting the NF-κB activation which results from the retrovirus infection. In conclusion, TCR peptide treatment and vitamin E supplementation effectively prevents immunodysfunction, excessive lipid peroxidation and free radical production, and antioxidant deficiency during murine AIDS. This may provide additional therapeutic approaches for treatment of human AIDS without additional immunotoxicity.