[8] ICOSLG, which is extensively expressed in both non-lymphatic and lymphatic tissues, is an important molecule in upregulating and promoting T cell immune responses.

The induced expression of ICOS on activated T cells mainly regulates the secretion of Th2 cytokines and thus shifts the immune response to the Th2 type.

[14] The strong impact of ICOS/ICOSLG interaction on T cell-mediated immune responses in vivo became evident by the disruption of the ICOS gene in mice.

In addition, blockade of ICOS/ICOSLG interaction in animal models of experimental allergic encephalomyelitis and of cardiac allograft rejection revealed a critical role of ICOS and its ligand in inflammatory immune reactions.

These defects contributed with altered adaptive immunity and neutropenia in patient, thus showing ICOSLG deficiency as a cause of combined immunodeficiency.

[15] The fluctuant balance between co-stimulatory and coinhibitory signals that a T cell receives participates in the initiation, effection, and termination of an immune response.

In view of its critical function in regulating immunohomeostasis, ICOS signaling has aroused great attention in immunodiagnosis and therapy.

[16] Stimulation of the ICOS pathway by tumor cell vaccine expressing ICOSLG, in combination with anti-CTLA-4 therapy blockade, led to enhanced antitumor efficacy.