Abstract
Coinhibitory molecules such as CTLA-4, PD-1 and BTLA negatively regulate immune responses. Multiple studies indicate that the deficiency or mutation of coinhibitory molecules leads to the development of autoimmune diseases in mice and humans, indicating that the negative signals from coinhibitory molecules are crucial for the prevention of autoimmunity. In some conditions, the administration of decoy coinhibitory receptors (e.g., CTLA-4 Ig) or mAb against coinhibitory molecules suppresses the responses of self-reactive T cells in autoimmune diseases. Therefore, modulation of coinhibitory signals seems to be an attractive approach to induce tolerance in autoimmune diseases in humans where the disease-inducing self-antigens are not known. Particularly, administration of CTLA-4 Ig has shown great promise in animal models of autoimmune diseases and has been gaining increasing attention in clinical investigation in several autoimmune diseases in humans.
Highlights
The immune system has developed multiple mechanisms to prevent harmful activation of immune cells
These results suggest that PD-L1 and PD-L2 differentially regulate the susceptibility and chronic progression of EAE in a strain specific manner
We have shown that the deficiency of B and T lymphocyte attenuator (BTLA) causes the breakdown of self-tolerance, resulting in the development of an autoimmune hepatitis- (AIH-) like disease and lymphocytic infiltration in multiple organs [75]
Summary
The immune system has developed multiple mechanisms to prevent harmful activation of immune cells. The ligand for BTLA is herpesvirus-entry mediator (HVEM), a TNF receptor family protein, and the ligation of BTLA with HVEM attenuates T-cell activation [6,7,8,9]. Since these inhibitory coreceptors inhibit proliferation and cytokine production of T cells in vitro and in vivo, they are thought to play important roles in maintaining immunological homeostasis and tolerance [10,11,12]. CD28-B7 interactions are important for the expansion and maintenance of CD4+CD25+ Tregs [17]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have