
CD28 and Tumor necrosis factor (TNF) co-stimulatory signals are required for recruitment and expansion of naïve T-cell, CD28 regulates both the development of T-regulatory cells in the Thymus and their peripheral homeostasis. These T-regulatory cells (CD25+ and CD4+) constitute 5-15% of the peripheral T-cells these cells are involved in the autoimmune disease as they act as immunosuppressant, studies shown that targeting of CD28 with monoclonal antibodies (mAbs) produces as significant increase in CD4 cell count in peripheral blood, spleen and the lymph nodes. In case of CD28, stimulatory mAbs act as artificial ligand that mimic the effect of natural ligands and cause co-stimulation of the T-cells and some of these mAbs have super agonistic activity. TeGenero, a German company, developed a recombinantly expressed humanized super agonist anti- CD28 mAbs (TGN1412). TGN1412 produced T-cell expansion in the absence of stimulation by T-cell receptor in the ex-vivo studies without provoking proinflammatory response; hence, TGN1412 shown to have the ability to activate regulatory T-cells therefore TGN1412 thought to possess a therapeutic effect in autoimmune disorders, and after extensive preclinical studies, TGN1412 approved for clinical trials. Unfortunately, the clinical trial does not went well as six of the volunteers suffered from severe adverse effects of the drug as discussed in this review.