Tuning Immune Suppression in Systemic Autoimmunity with Self-Derived Peptides

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 antigenderived 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.