Co-stimulation by ICOS

ICOS (Inducible T-cell COStimulator) is a critical costimulatory receptor that enhances T cell responses following initial activation. Unlike CD28, which is constitutively expressed on naive T cells, ICOS expression is induced upon T cell activation. Both ICOS and CD28 engage class IA phosphatidylinositol 3-kinase (PI3K), leading to the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and activation of downstream signaling pathways, including AKT. However, ICOS signaling is distinguished by a stronger induction of PIP3 production and more robust AKT phosphorylation compared to CD28 signaling. This enhanced signaling through ICOS contributes to its unique role in promoting T cell survival, cytokine production, and differentiation, particularly in the context of T follicular helper (Tfh) cell development and function. Despite these similarities, detailed knowledge about ICOS-specific downstream signaling pathways remains limited, highlighting a key area for further research to fully understand its distinct and overlapping roles with CD28 in T cell immunity.

Summary from Reactome (R-HSA-9927354), read 2026-09-23.