ICOS

Full name: Inducible T-cell costimulator

Aliases:1 AILIM, CD278, and CVID1

Size:2 55–60 kDa

Family:1,2 CD28 and CTLA-4 cell-surface receptor family of costimulatory molecules

Receptors:1 CD28 and CTLA-4 cell-surface receptor family

Major cellular sources:2-6 Activated and germinal center T cells and naïve T cells

Major cellular targets:5-8 Th-cell cytokines, including IFN-γ, TNF-α, IL-4, IL-5, IL-10, and IL-13

Disease states associated with:6 Systemic lupus erythematosus

Major physiologic functions:

  • ICOS is expressed on activated and germinal center T cells and interacts with its only known ligand, ICOS-L.2-6

  • ICOS forms homodimers and plays an important role in cell-cell signaling, immune responses, and regulation of cell proliferation.1,2

  • ICOS is either absent or expressed at very low levels on naïve T cells, but it is upregulated upon stimulation, suggesting that its costimulatory role is more important for memory and effector T cells.7

  • ICOS/ICOS-L costimulation plays a role in the production of certain Th-cell cytokines, including IFN-γ, TNF-α, IL-4, IL-5, IL-10, and IL-13, and promotes the migration, development, and activation of lymphocytes as well as antibodies produced by B cells.6-8

  • ICOS is an essential mediator of Th2-cell function in humoral immune responses.5

AILIM: activation-inducible lymphocyte immuno-mediatory molecule; CD: cluster of differentiation; CTLA-4: cytotoxic T-lymphocyte antigen–4; CVID: common variable immunodeficiency; ICOS-L: ICOS ligand; IFN-γ: interferon gamma; IL: interleukin; Th: T helper; TNF: tumor necrosis factor.

References:

  • 1.

    NCBI. Gene. ICOS inducible T cell costimulator [Homo sapiens (human)]. www.ncbi.nlm.nih.gov/gene/29851. Accessed March 11, 2021.

  • 2.

    Mages HW, Hutloff A, Heuck C, et al. Eur J Immunol. 2000;30:1040-1047.​

  • 3.

    Coyle AJ, Lehar S, Lloyd C, et al. Immunity. 2000;13:95-105.

  • 4.

    Dong C, Juedes AE, Temann UA, et al. Nature. 2001;409:97-101.​

  • 5.

    Dong C, Temann UA, Flavell RA. J Immunol. 2001;166:3659-3662.

  • 6.

    Wikenheiser DJ, Stumhofer JS. Front Immunol. 2016;7:304.​

  • 7.

    Frauwirth KA, Thompson CB. J Clin Invest. 2002;109:295-299.

  • 8.

    Vieira PL, Wassink L, Smith LM, et al. Eur J Immunol. 2004;34:1282-1290.