CD278

Inducible T-cell co-stimulator, also known as ICOS, is a human gene.cite web | title = Entrez Gene: ICOS inducible T-cell co-stimulator| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29851| accessdate = ]

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 T_h2 cells in particular.cite journal | author = Rudd CE, Schneider H | title = Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling | journal = Nat. Rev. Immunol. | volume = 3 | issue = 7 | pages = 544–56 | year = 2003 | pmid = 12876557 | doi = 10.1038/nri1131 | issn = ] cite journal | author = Dong C, Juedes AE, Temann UA, Shresta S, Allison JP, Ruddle NH, Flavell RA | title = ICOS co-stimulatory receptor is essential for T-cell activation and function | journal = Nature | volume = 409 | issue = 6816 | pages = 97–101 | year = 2001 | pmid = 11343121 | doi = 10.1038/35051100 | issn = ]

PBB_Summary
section_title =
summary_text = 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.cite web | title = Entrez Gene: ICOS inducible T-cell co-stimulator| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29851| accessdate = ]

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.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Flesch IE |title=Inducible costimulator (ICOS). |journal=J. Biol. Regul. Homeost. Agents |volume=16 |issue= 3 |pages= 214–6 |year= 2003 |pmid= 12456021 |doi=
*cite journal | author=Shilling RA, Bandukwala HS, Sperling AI |title=Regulation of T:B cell interactions by the inducible costimulator molecule: does ICOS "induce" disease? |journal=Clin. Immunol. |volume=121 |issue= 1 |pages= 13–8 |year= 2006 |pmid= 16790364 |doi= 10.1016/j.clim.2006.04.574
*cite journal | author=Hutloff A, Dittrich AM, Beier KC, "et al." |title=ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. |journal=Nature |volume=397 |issue= 6716 |pages= 263–6 |year= 1999 |pmid= 9930702 |doi= 10.1038/16717
*cite journal | author=Yoshinaga SK, Whoriskey JS, Khare SD, "et al." |title=T-cell co-stimulation through B7RP-1 and ICOS. |journal=Nature |volume=402 |issue= 6763 |pages= 827–32 |year= 2000 |pmid= 10617205 |doi= 10.1038/45582
*cite journal | author=Ling V, Wu PW, Finnerty HF, "et al." |title=Cutting edge: identification of GL50, a novel B7-like protein that functionally binds to ICOS receptor. |journal=J. Immunol. |volume=164 |issue= 4 |pages= 1653–7 |year= 2000 |pmid= 10657606 |doi=
*cite journal | author=Aicher A, Hayden-Ledbetter M, Brady WA, "et al." |title=Characterization of human inducible costimulator ligand expression and function. |journal=J. Immunol. |volume=164 |issue= 9 |pages= 4689–96 |year= 2000 |pmid= 10779774 |doi=
*cite journal | author=Machado RD, Pauciulo MW, Fretwell N, "et al." |title=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. |journal=Genomics |volume=68 |issue= 2 |pages= 220–8 |year= 2001 |pmid= 10964520 |doi= 10.1006/geno.2000.6291
*cite journal | author=Tezuka K, Tsuji T, Hirano D, "et al." |title=Identification and characterization of rat AILIM/ICOS, a novel T-cell costimulatory molecule, related to the CD28/CTLA4 family. |journal=Biochem. Biophys. Res. Commun. |volume=276 |issue= 1 |pages= 335–45 |year= 2000 |pmid= 11006126 |doi= 10.1006/bbrc.2000.3466
*cite journal | author=Wang S, Zhu G, Chapoval AI, "et al." |title=Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS. |journal=Blood |volume=96 |issue= 8 |pages= 2808–13 |year= 2000 |pmid= 11023515 |doi=
*cite journal | author=Breitfeld D, Ohl L, Kremmer E, "et al." |title=Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. |journal=J. Exp. Med. |volume=192 |issue= 11 |pages= 1545–52 |year= 2001 |pmid= 11104797 |doi=
*cite journal | author=Beier KC, Hutloff A, Dittrich AM, "et al." |title=Induction, binding specificity and function of human ICOS. |journal=Eur. J. Immunol. |volume=30 |issue= 12 |pages= 3707–17 |year= 2001 |pmid= 11169414 |doi=
*cite journal | author=Ling V, Wu PW, Finnerty HF, "et al." |title=Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches. |journal=Genomics |volume=78 |issue= 3 |pages= 155–68 |year= 2002 |pmid= 11735222 |doi= 10.1006/geno.2001.6655
*cite journal | author=Lee YH, Ji JD, Sohn J, Song GG |title=Polymorphsims of CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter -670 in spondyloarthropathies. |journal=Clin. Rheumatol. |volume=20 |issue= 6 |pages= 420–2 |year= 2002 |pmid= 11771526 |doi=
*cite journal | author=Haimila KE, Partanen JA, Holopainen PM |title=Genetic polymorphism of the human ICOS gene. |journal=Immunogenetics |volume=53 |issue= 12 |pages= 1028–32 |year= 2002 |pmid= 11904679 |doi= 10.1007/s00251-002-0431-2
*cite journal | author=Wang S, Zhu G, Tamada K, "et al." |title=Ligand binding sites of inducible costimulator and high avidity mutants with improved function. |journal=J. Exp. Med. |volume=195 |issue= 8 |pages= 1033–41 |year= 2002 |pmid= 11956294 |doi=
*cite journal | author=Riley JL, Mao M, Kobayashi S, "et al." |title=Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 18 |pages= 11790–5 |year= 2002 |pmid= 12195015 |doi= 10.1073/pnas.162359999
*cite journal | author=Witsch EJ, Peiser M, Hutloff A, "et al." |title=ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells. |journal=Eur. J. Immunol. |volume=32 |issue= 9 |pages= 2680–6 |year= 2002 |pmid= 12207353 |doi= 10.1002/1521-4141(200209)32:9<2680::AID-IMMU2680>3.0.CO;2-6 |doilabel=10.1002/1521-4141(200209)32:92680::AID-IMMU26803.0.CO;2-6
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Grimbacher B, Hutloff A, Schlesier M, "et al." |title=Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. |journal=Nat. Immunol. |volume=4 |issue= 3 |pages= 261–8 |year= 2003 |pmid= 12577056 |doi= 10.1038/ni902

External links

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References

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

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