title: CD28 signals the differential control of regulatory T cells and effector T cells.
abstract: One possible means of driving antigen-specific immune suppression is to expand or induce antigen-specific FoxP3-expressing Treg cells. One way of activating and expanding these specialized cells, both in vitro and in vivo, is by strong costimulation via CD28 with an agonistic anti-CD28 monoclonal antibody, called anti-CD28 superagonist (CD28SA). However, CD28SA also strongly activates conventional T (Tconv) cells to secrete proinflammatory cytokines and, under certain conditions, causes serious cytokine release syndrome. In this issue of European Journal of Immunology, Tabares et al. [Eur. J. Immunol. 2014. 44: 1225-1236] address how CD28SA can be used for the differential control of human Treg and Tconv cells to suppress immune responses without serious adverse effects. They show that, depending on the dose of the antibody or by comedication of cortico-steroid, the selective expansion of Treg cells can be achieved without significantly activating Tconv cells to produce inflammatory cytokines. This difference in CD28 signal sensitivity between the two populations can be exploited for better control of immune responses.
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Mikami
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018106:CD28 Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018106:CD28 Antigens; C509303:TGN-1412
keywords: CD28; Immune suppression; Regulatory T cells