CD28 superagonists put a break on autoimmunity by preferentially activating CD4+CD25+ regulatory T cells

There is strong evidence that a quantitative and/or functional deficiency in CD4(+)CD25(+) regulatory T cells (T-reg cells) plays a key role in the pathogenesis of many human autoimmune diseases. Therefore, targeting regulatory T cells with novel forms of immunotherapy should provide a means for successfully battling autoimmunity in humans. We have recently shown that superagonistic monoclonal antibodies with specificity for CD28 (CD28 superagonists) are capable of activating and preferentially expanding T-reg cells over conventional T cells in vitro and, importantly, also in vivo. Moreover, therapeutic application of CD28 superagonists elicited profound therapeutic effects in various animal models of autoimmunity, including experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA) of the Lewis rat. Adoptive transfer experiments with T-reg cells from CD28 superagonist-treated rats proved that protection from EAE is, indeed, mediated by CD28 superagonist-activated T-reg cells. Therefore, effective targeting of CD4+CD25+ regulatory T cells makes CD28 superagonists a promising novel tool for the treatment of human autoimmune diseases. (C) 2005 Elsevier B.V. All rights reserved.