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lüll Superagonistic anti-CD28 antibodies: potent activators of regulatory T cells for the therapy of autoimmune diseases Beyersdorf N; Hanke T; Kerkau T; Hunig TAnn Rheum Dis 2005[Nov]; 64 Suppl 4 (Suppl 4): iv91-5This paper reviews the existing evidence regarding the use of superagonistic anti-CD28 antibodies (CD28 superagonists) for therapeutic manipulation of regulatory T cells (T(reg) cells). The molecular properties of superagonistic anti-CD28 antibodies allow the generation of a strong activating signal in mature T cells, including T(reg) cells, without additional stimulation of the T cell receptor complex. CD28 superagonist administration in vivo leads to the preferential expansion and strong activation of naturally occurring CD4+CD25+CTLA-4+FoxP3+ T(reg) cells over conventional T cells. In animal models, both prophylactic and therapeutic administration of a CD28 superagonist prevented or at least greatly mitigated clinical symptoms and induced remission. Adoptive transfer experiments have further shown that CD28 superagonists mediate protection by expansion and activation of CD4+CD25+ T(reg) cells. Therefore, superagonistic anti-CD28 antibodies offer a promising novel treatment option for human autoimmune diseases and the first clinical trials are eagerly awaited.|Animals[MESH]|Antibodies, Monoclonal/immunology/*therapeutic use[MESH]|Autoimmune Diseases/immunology/*therapy[MESH]|CD28 Antigens/*immunology[MESH]|Humans[MESH]|Interleukin-2/immunology[MESH]|Lymphocyte Activation/immunology[MESH]|Rats[MESH]|T-Lymphocytes, Regulatory/*immunology[MESH] |