Immunomodulation by immunopeptides and autoantibodies in aging, autoimmunity, and infection.
The operation of the immune system is a complex orchestration of specific self and non-self-recognition capacities mediated by cells of the innate system acting in coordination with T and B lymphocytes in a series of processes modulated by cytokines. We provide evidence for a natural immunomodulatory system involving autoantibodies directed against a controlling segment of T cell receptor Vbeta chains that downregulate production of stimulatory cytokines balanced by the peptides which in turn upregulate inflammatory activities mediated by TH1-type helper cells. TCR Vbeta-derived peptides effective in retrovirally induced immunosupression could also reverse the effects of immunosenescence in aged mice by restoring the balance of TH1- and TH2-type immunity and the resistance of the animals to cardiac pathology caused by infection with coxsackievirus. An unexpected finding was an adaptive role of the T cells from peptide-treated mice in remodeling damaged hearts by increasing net collagen synthesis by cardiac fibroblasts.
Marchalonis
J J
JJ
Department of Microbiology and Immunology, College of Medicine, University of Arizona, 1501 N. Campbell Avenue, Tucson, Arizona 85724, USA. marchjj@email.arizona.edu
Schluter
S F
SF
Sepulveda
R T
RT
Watson
R R
RR
Larson
D F
DF
D000375:Aging / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D029822:Enterovirus B, Human / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000502:physiology*; D007155:Immunologic Factors / Q000378:metabolism*; D007239:Infections / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000473:pathology; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000276:immunology; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D007155:Immunologic Factors; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta