T cell receptor V beta complementarity-determining region 1 peptide administration moderates immune dysfunction and cytokine dysregulation induced by murine retrovirus infection.
Murine AIDS, induced by LP-BM5 murine leukemia retrovirus infection, causes a progressive and profound immunodeficiency in female C57B1/6 mice. Previously, we reported that autoantibodies were elevated during the initiation phases of this murine retrovirus infection and bound peptide determinants corresponding to CDR1 of several TCR V beta-chains. Therefore, we designed studies to determine whether administration of a major autoimmunogenic TCR V beta CDR1 peptide before or after infection with LP-BM5 retrovirus would modulate retrovirus-induced dysregulation of T cell function. Administration of the TCR V beta CDR1 peptide before murine retrovirus infection significantly prevented its suppression of splenic NK cell activity, T and B cell proliferation, and monokine (IL-6 and TNF-alpha) and Th1 cytokine (IL-2 and IFN-gamma) release by splenocytes, and inhibited retrovirus-induced elevation of Th2 cytokine (IL-5 and IL-10). Similar data were obtained with peptide immunization 2 wk after murine retrovirus infection at 6 and 16 wk postinfection. However, delaying peptide immunization until severe suppression of T and B cell mitogenesis had occurred did not restore their functions. Immunization with TCR V beta peptide prevents development of retrovirus-induced immune dysfunction, which suggests a possible pathogenic role of autoreactive T cells as regulatory elements.
Watson
R R
RR
Department of Family and Community Medicine, University of Arizona College of Medicine, Tucson 85724, USA.
Wang
J Y
JY
Dehghanpisheh
K
K
Huang
D S
DS
Wood
S
S
Ardestani
S K
SK
Liang
B
B
Marchalonis
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta