[1] In the case of T cells, two stimuli are required to fully activate their immune response.
During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response.
[2] The surface expression of different co-stimulatory molecules is regulated on a transcriptional and post-transcriptional level, but also by endocytosis.
It is constitutively localized, among other important T cell signaling molecules, in the central SMAC (supramolecular activation complex) of the immunological synapse.
[2][6] Signaling through co-stimulatory molecules from TNFRSF often involves the interaction with TRAF adaptor proteins to enhance T cell stimulation.
[5] OX40 (CD134; TNFRSF4) is another co-stimulatory molecule expressed after T cell activation, but in the later timepoints, since it inhibits apoptosis and increases survival rate several days after the stimulation.
[9] The differentiation of T helper cells (TH) into different subsets also partially depends on their co-stimulatory molecules.
[2][4][6] Effector T cells are mainly regulated by TNFRSF molecules, such as 41-BB, CD27, OX40, DR3 or GITR, which enhance their proliferation and survival.
Apart from CD28; ICOS, 41-BB, OX40, TIM3, CD30, BTLA or CD27 were also shown to play role in the proper formation and later signaling of TM.
[15] Abatacept (Orencia) is a T cell co-stimulation modulator approved for the treatment of rheumatoid arthritis.
The cytokines secreted by activated T cells are thought to both initiate and propagate the immunologically driven inflammation associated with rheumatoid arthritis.
Orencia, a soluble fusion protein, works by altering the co-stimulatory signal required for full T-cell activation.
A new co-stimulatory superagonistic drug, TGN1412, was the subject of a clinical trial at Northwick Park Hospital, London.