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 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.