Inducible T-cell co-stimulator
, also known as ICOS
, is a human 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 Th2 cells in particular.
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(1). The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due to reduced IL-2 secretion. 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 Freunds 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 Th2 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.
11111 C. Dong, A. E. Juedes, U. A. Temann et al., Nature 409 (6816), 97 (2001).