CD278

Inducible T-cell co-stimulator
Identifiers
Symbols	ICOS ; AILIM; CD278; CVID1
External IDs	OMIM: 604558 MGI: 1858745 HomoloGene: 8097 GeneCards: ICOS Gene
Gene ontology Cellular component • extracellular region • plasma membrane • integral component of plasma membrane • external side of plasma membrane Biological process • T cell tolerance induction • immune response • single organismal cell-cell adhesion • T cell costimulation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	29851	54167
Ensembl	ENSG00000163600	ENSMUSG00000026009
UniProt	Q9Y6W8	Q9WVS0
RefSeq (mRNA)	NM_012092	NM_017480
RefSeq (protein)	NP_036224	NP_059508
Location (UCSC)	Chr 2: 203.94 – 203.96 Mb	Chr 1: 60.98 – 61 Mb
PubMed search	[1]	[2]

Inducible T-cell costimulator is an immune checkpoint protein that in humans is encoded by the ICOS gene.

CD278 or ICOS (Inducible T-cell COStimulator) is a CD28-superfamily costimulatory molecule that is expressed on activated T cells. It is thought to be important for T_h2 cells in particular.

Function

The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses, and regulation of cell proliferation.

ICOS knockout phenotype

Compared to wild-type naïve T cells, ICOS-/- T cells activated with plate-bound anti-CD3 have reduced proliferation and IL-2 secretion. The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due either to ICOS-mediated IL-2 secretion or the activation of similar signaling pathways between ICOS and IL-2. In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell activated in vitro have reduced IL-4 secretion, but similar IFN-g secretion. Similarly, CD4+ T cells purified from ICOS-/- mice immunized with the protein keyhole limpet hemocyanin (KLH) in alum or Complete Freund's Adjuvant have attenuated IL-4 secretion, but similar IFN-g and IL-5 secretion when recalled with KLH.

These data are similar to an airway hypersensitivity model showing similar IL-5 secretion, but reduced IL-4 secretion in response to sensitization with Ova protein, indicating a defect in Th2 cytokine secretion, but not a defect in Th1 differentiation as both IL-4 and IL-5 are Th2-associated cytokines. In agreement with reduced Th2 responses, ICOS-/- mice have reduced germinal center formation and IgG1 and IgE antibody titers in response to immunization.

Combination therapy

Ipilimumab patients expressed increased ICOS+ T cells in tumor tissues and blood. The increase served as a pharmacodynamic biomarker of anti-CTLA-4 treatment. In wild-type C57BL/6 mice, anti-CTLA-4 treatment resulted in tumor rejection in 80 to 90% of subjects, but in gene-targeted mice that were deficient for either ICOS or its ligand, the efficacy was less than 50%. An agonistic stimulus for the ICOS pathway during anti-CTLA-4 therapy resulted in an increase in efficacy that was about four to five times as large as that of control treatments. As of 2015 antibodies for ICOS were not available for clinical testing.

External links

• ICOS protein at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.