T-cell COStimulator (ICOS) is a T cell costimulatory molecule of the CTLA4/PD1/CD28 family, and plays a nonoverlapping function with CD28 on CD4+ T cells.
An Overview of ICOS
ICOS is a newly discovered costimulatory molecule. The costimulatory signal provided by ICOS on activated T cells can promote the proliferation of T cells, regulate the differentiation of T cells, and maintain the effect and function of activated T cells (including memory T cells). ICOS is a member of immunoglobulin superfamily, which is composed of 199 amino acids and is divided into three parts: extracellular Ig-V-like domain, transmembrane domain and cytoplasmic tail. ICOS, as a costimulatory molecule, is expressed only on activated T cells, promoting T cell differentiation and exerting effect. In addition, ICOS can protect memory T cells from apoptosis and promote T cell proliferation and cytokine secretion.
Major types of ICOS
The type of ICOS is the CTLA4/PD1/CD28 family, which is mainly expressed in activated Th2 cells. The ligands are human B7-H2 / ICOSL and mouse B7-associated protein 1 (B7RP-1) and up-regulate the expression of adhesion molecules and cytokines in activated Th2 cells. Meanwhile, they also promote B cells to differentiate into plasma cells and produce antibodies.
Agonist of ICOS
The expression of ICOS could be upregulated by PMA-CD28. It was found that only a small amount of ICOS expression was observed in CD4 T cells stimulated by PMA and calcium carrier alone, while the combination of PMA and calcium carrier could induce the sustained expression of ICOS. The expression of ICOS decreased to the level of PMA alone after combined stimulation with cyclosporin A. CD28 costimulation enhanced the expression of ICOS, but decreased the up-regulation of ICOS when B7-1/B7-2 was absent, and the expression of ICOS was not completely dependent on the signal of CD28.
ICOS and Diseases
ICOS plays a dual role in tumor immunity. On the one hand, ICOS can promote the proliferation of CD8 T cells and the production of cytokines such as IL-2, thereby enhancing the anti-tumor immune effect; on the other hand, ICOS inhibits tumor immunity by inhibiting CD4 T proliferation through IL-10/TGF-β. The immunomodulation targeting ICOS pathway has important clinical significance in the development of long-term tolerance including autoimmune diseases and transplantation immunity.
Cheng sa, Gao Jimin. A. (2016). Biological characteristics of ICOS on regulatory T cells in peripheral blood of healthy people. Chinese Journal of Immunology. 32（12）；1753-1757