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Inducible T-cell co-stimulator
Symbols ICOS; AILIM; CD278; MGC39850
External IDs OMIM604558 MGI1858745 HomoloGene8097 GeneCards: ICOS Gene
RNA expression pattern
PBB GE ICOS 210439 at tn.png
More reference expression data
Species Human Mouse
Entrez 29851 54167
Ensembl ENSG00000163600 ENSMUSG00000026009
UniProt Q9Y6W8 Q3V3X2
RefSeq (mRNA) NM_012092 NM_017480
RefSeq (protein) NP_036224 NP_059508
Location (UCSC) Chr 2:
204.51 - 204.53 Mb
Chr 1:
60.92 - 60.94 Mb
PubMed search [1] [2]

Inducible T-cell costimulator is a protein that in humans is encoded by the ICOS gene.[1][2][3]

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.[4][5]

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.[3]


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.


  1. ^ 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". Nature 397 (6716): 263-6. doi:10.1038/16717. PMID 9930702.  
  2. ^ 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". Nature 402 (6763): 827-32. doi:10.1038/45582. PMID 10617205.  
  3. ^ a b "Entrez Gene: ICOS inducible T-cell co-stimulator".  
  4. ^ Rudd CE, Schneider H (2003). "Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling". Nat. Rev. Immunol. 3 (7): 544–56. doi:10.1038/nri1131. PMID 12876557.  
  5. ^ Dong C, Juedes AE, Temann UA, Shresta S, Allison JP, Ruddle NH, Flavell RA (2001). "ICOS co-stimulatory receptor is essential for T-cell activation and function". Nature 409 (6816): 97–101. doi:10.1038/35051100. PMID 11343121.  

Further reading

  • Flesch IE (2003). "Inducible costimulator (ICOS).". J. Biol. Regul. Homeost. Agents 16 (3): 214–6. PMID 12456021.  
  • 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. PMID 16790364.  
  • 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. PMID 10657606.  
  • 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. PMID 10779774.  
  • 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.". Genomics 68 (2): 220–8. doi:10.1006/geno.2000.6291. PMID 10964520.  
  • 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. PMID 11006126.  
  • Wang S, Zhu G, Chapoval AI, et al. (2000). "Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS.". Blood 96 (8): 2808–13. PMID 11023515.  
  • Breitfeld D, Ohl L, Kremmer E, et al. (2001). "Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production.". J. Exp. Med. 192 (11): 1545–52. doi:10.1084/jem.192.11.1545. PMID 11104797.  
  • Beier KC, Hutloff A, Dittrich AM, et al. (2001). "Induction, binding specificity and function of human ICOS.". Eur. J. Immunol. 30 (12): 3707–17. doi:10.1002/1521-4141(200012)30:12<3707::AID-IMMU3707>3.0.CO;2-Q. PMID 11169414.  
  • 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.". Genomics 78 (3): 155–68. doi:10.1006/geno.2001.6655. PMID 11735222.  
  • 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. PMID 11771526.  
  • Haimila KE, Partanen JA, Holopainen PM (2002). "Genetic polymorphism of the human ICOS gene.". Immunogenetics 53 (12): 1028–32. doi:10.1007/s00251-002-0431-2. PMID 11904679.  
  • Wang S, Zhu G, Tamada K, et al. (2002). "Ligand binding sites of inducible costimulator and high avidity mutants with improved function.". J. Exp. Med. 195 (8): 1033–41. doi:10.1084/jem.20011607. PMID 11956294.  
  • Riley JL, Mao M, Kobayashi S, et al. (2002). "Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors.". Proc. Natl. Acad. Sci. U.S.A. 99 (18): 11790–5. doi:10.1073/pnas.162359999. PMID 12195015.  
  • Witsch EJ, Peiser M, Hutloff A, et al. (2002). "ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells.". Eur. J. Immunol. 32 (9): 2680–6. doi:10.1002/1521-4141(200209)32:9<2680::AID-IMMU2680>3.0.CO;2-6. PMID 12207353.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • 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. PMID 12577056.  

External links

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


11111 C. Dong, A. E. Juedes, U. A. Temann et al., Nature 409 (6816), 97 (2001).



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