title: Tuning immune suppression in systemic autoimmunity with self-derived peptides.
abstract: A central pathologic mechanism in systemic autoimmune diseases with chronic inflammation such as systemic lupus erythematosus (SLE) is the aberrant production of antibodies against self-components produced by abnormal B cells with the help of hyperactive CD4(+)T cells. One goal for better control of the disease is the limitation of the number of abnormal and hyperactive cells, to prevent and/or attenuate the damaging effects of the pathogenic antibodies on target tissues. Recently, a role of regulatory T cells in the suppression of autoimmune reactivity in diseases including SLE has been recognized. CD4(+)CD25(+) regulatory T cells (Tregs) and CD8(+) inhibitory T (Ti) cells have been found numerically decreased and/or functionally impaired in some patients with active systemic lupus erythematosus. Recent experimental work and preclinical studies have also provided proof-of-concept for the possibility of induction of self-tolerance through the modulation of regulatory/suppressor T cells using self antigen-derived peptides that could promote suppression of the production of pathogenic antibodies. This review explores the mechanisms elicited by the administration of self antigen-derived peptides on the induction of suppression of autoimmune responses, and how this information might lead to future development of new strategies for better management of systemic autoimmune conditions.
authors.affiliation: Division of Rheumatology, David Geffen School of Medicine, University of California Los Angeles, 1000 Veteran Avenue 32-59, Los Angeles, CA 90095-1670, USA. RPSingh@mednet.ucla.edu
authors.forename: Ram Pyare
authors.initials: RP
authors.lastname: Singh
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D018106:CD28 Antigens; D007166:Immunosuppressive Agents; D010455:Peptides; D016212:Transforming Growth Factor beta