title: Vitamin E deficiency and immune dysfunction in retrovirus-infected C57BL/6 mice are prevented by T-cell receptor peptide treatment.
abstract: Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine acquired immunodeficiency syndrome (AIDS), which is functionally similar to human AIDS. Retrovirus infection inhibited release of T-helper 1 cytokines, stimulated secretion of T-helper 2 cytokines and induced hepatic and cardiac vitamin E deficiency with increased lipid peroxides. We hypothesized that the immune dysfunction caused increased oxidation and loss of vitamin E. Because T-cell receptor (TCR) peptide treatment blocked the excessive stimulation of a T-cell subset by retroviral superantigens, we tested whether maintenance of normal immune function during infection prevented excessive oxidative damage. The TCR peptide treatments with doses > 100 microgram/mouse and administered 2-4 wk postinfection significantly inhibited the retrovirus-induced immune dysfunction, concomitantly reduced tissue oxidative damage and thereby largely maintained vitamin E concentration in the liver and heart. Reducing the dose of peptide or delaying administration until early murine AIDS had developed resulted in severe immune dysfunction that caused elevated tissue lipid peroxidation and loss of vitamin E. The TCR peptide treatment partially maintained production of interleukin-2 (IL-2) and prevented retrovirus-induced elevated production of IL-6 by splenocytes in vitro. In conclusion, TCR peptide treatment during murine retrovirus infection ameliorated immune dysfunction and thus prevented increases in tissue lipid peroxidation and vitamin E loss. T-cell immune dysfunction and its prevention by TCR peptide treatment is important in the therapy of vitamin E deficiency induced by retrovirus infection.
authors.affiliation: Arizona Prevention Center, University of Arizona, Tucson, 85724, USA.
authors.forename: B
authors.initials: B
authors.lastname: Liang
authors.forename: S
authors.initials: S
authors.lastname: Ardestani
authors.forename: H H
authors.initials: HH
authors.lastname: Chow
authors.forename: C
authors.initials: C
authors.lastname: Eskelson
authors.forename: R R
authors.initials: RR
authors.lastname: Watson
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight / Q000502:physiology; D005260:Female; D007107:Immune System / Q000503:physiopathology*; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000627:therapeutic use*; D011897:Random Allocation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000502:physiology*; D014810:Vitamin E / Q000032:analysis / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D015850:Interleukin-6; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014810:Vitamin E