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.
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.
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 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 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 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.
^Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, Kroczek RA (Feb 1999). "ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28". Nature397 (6716): 263–6. doi:10.1038/16717. PMID9930702.
^Yoshinaga SK, Whoriskey JS, Khare SD, Sarmiento U, Guo J, Horan T, Shih G, Zhang M, Coccia MA, Kohno T, Tafuri-Bladt A, Brankow D, Campbell P, Chang D, Chiu L, Dai T, Duncan G, Elliott GS, Hui A, McCabe SM, Scully S, Shahinian A, Shaklee CL, Van G, Mak TW, Senaldi G (Jan 2000). "T-cell co-stimulation through B7RP-1 and ICOS". Nature402 (6763): 827–32. doi:10.1038/45582. PMID10617205.
Shilling RA, Bandukwala HS, Sperling AI (2006). "Regulation of T:B cell interactions by the inducible costimulator molecule: does ICOS "induce" disease?". Clin. Immunol.121 (1): 13–8. doi:10.1016/j.clim.2006.04.574. PMID16790364.
Ling V, Wu PW, Finnerty HF et al. (2000). "Cutting edge: identification of GL50, a novel B7-like protein that functionally binds to ICOS receptor.". J. Immunol.164 (4): 1653–7. doi:10.4049/jimmunol.164.4.1653. PMID10657606.CS1 maint: Explicit use of et al. (link)
Aicher A, Hayden-Ledbetter M, Brady WA et al. (2000). "Characterization of human inducible costimulator ligand expression and function.". J. Immunol.164 (9): 4689–96. doi:10.4049/jimmunol.164.9.4689. PMID10779774.CS1 maint: Explicit use of et al. (link)
Machado RD, Pauciulo MW, Fretwell N et al. (2001). "A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. The International PPH Consortium.". Genomics68 (2): 220–8. doi:10.1006/geno.2000.6291. PMID10964520.CS1 maint: Explicit use of et al. (link)
Tezuka K, Tsuji T, Hirano D et al. (2000). "Identification and characterization of rat AILIM/ICOS, a novel T-cell costimulatory molecule, related to the CD28/CTLA4 family.". Biochem. Biophys. Res. Commun.276 (1): 335–45. doi:10.1006/bbrc.2000.3466. PMID11006126.CS1 maint: Explicit use of et al. (link)
Wang S, Zhu G, Chapoval AI et al. (2000). "Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS.". Blood96 (8): 2808–13. PMID11023515.CS1 maint: Explicit use of et al. (link)
Ling V, Wu PW, Finnerty HF et al. (2002). "Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches.". Genomics78 (3): 155–68. doi:10.1006/geno.2001.6655. PMID11735222.CS1 maint: Explicit use of et al. (link)
Lee YH, Ji JD, Sohn J, Song GG (2002). "Polymorphsims of CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter -670 in spondyloarthropathies.". Clin. Rheumatol.20 (6): 420–2. doi:10.1007/s100670170007. PMID11771526.
Grimbacher B, Hutloff A, Schlesier M et al. (2003). "Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency.". Nat. Immunol.4 (3): 261–8. doi:10.1038/ni902. PMID12577056.CS1 maint: Explicit use of et al. (link)