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ICOS Deficiency

  • Ulrich SalzerEmail author
Chapter
Part of the Rare Diseases of the Immune System book series (RDIS)

Abstract

Inducible costimulator (ICOS) deficiency is an autosomal recessive inherited primary immunodeficiency and was the first monogenetic defect described in common variable immunodeficiency. ICOS-deficient patients have high rates of immunedysregulatory complications, and bacterial, viral and opportunistic infections. Immunoglobulin substitution and antibiotic treatment of breakthrough infections are the mainstays of treatment in ICOS deficiency. In cases of conventional treatment failure, hematopoietic stem cell transplantation may be considered.

Keywords

ICOS T cells Costimulation CVID B cells 

References

  1. 1.
    Carreno BM, Collins M. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu Rev Immunol. 2002;20:29–53.CrossRefGoogle Scholar
  2. 2.
    Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515–48.CrossRefGoogle Scholar
  3. 3.
    Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol. 2002;2:116–26.CrossRefGoogle Scholar
  4. 4.
    Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, Kroczek RA. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature. 1999;397:263–6.CrossRefGoogle Scholar
  5. 5.
    Swallow MM, Wallin JJ, Sha WC. B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFalpha. Immunity. 1999;11:423–32.CrossRefGoogle Scholar
  6. 6.
    Coyle AJ, Lehar S, Lloyd C, Tian J, Delaney T, Manning S, Nguyen T, Burwell T, Schneider H, Gonzalo JA, Gosselin M, Owen LR, Rudd CE, Gutierrez-Ramos JC. The CD28-related molecule ICOS is required for effective T cell-dependent immune responses. Immunity. 2000;13:95–105.CrossRefGoogle Scholar
  7. 7.
    Ling V, Wu PW, Finnerty HF, Agostino MJ, Graham JR, Chen S, Jussiff JM, Fisk GJ, Miller CP, Collins M. Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches. Genomics. 2001;78:155–68.CrossRefGoogle Scholar
  8. 8.
    Beier KC, Hutloff A, Dittrich AM, Heuck C, Rauch A, Büchner K, Ludewig B, Ochs HD, Mages HW, Kroczek RA. Induction, binding specificity and function of human ICOS. Eur J Immunol. 2000;30:3707–17.CrossRefGoogle Scholar
  9. 9.
    Okamoto N, Tezuka K, Kato M, Abe R, Tsuji T. PI3-kinase and MAP-kinase signaling cascades in AILIM/ICOS- and CD28-costimulated T-cells have distinct functions between cell proliferation and IL-10 production. Biochem Biophys Res Commun. 2003;310:691–702.CrossRefGoogle Scholar
  10. 10.
    Parry RV, Rumbley CA, Vandenberghe LH, June CH, Riley JL. CD28 and inducible costimulatory protein Src homology 2 binding domains show distinct regulation of phosphatidylinositol 3-kinase, Bcl-xL, and IL-2 expression in primary human CD4 T lymphocytes. J Immunol. 2003;171:166–74.CrossRefGoogle Scholar
  11. 11.
    Yagi J, Arimura Y, Dianzani U, Uede T, Okamoto T, Uchiyama T. Regulatory roles of IL-2 and IL-4 in H4/inducible costimulator expression on activated CD4+ T cells during Th cell development. J Immunol. 2003;171:783–94.CrossRefGoogle Scholar
  12. 12.
    Wassink L, Vieira PL, Smits HH, Kingsbury GA, Coyle AJ, Kapsenberg ML, Wierenga EA. ICOS expression by activated human Th cells is enhanced by IL-12 and IL-23: increased ICOS expression enhances the effector function of both Th1 and Th2 cells. J Immunol. 2004;173:1779–86.CrossRefGoogle Scholar
  13. 13.
    Vinuesa CG, Cook MC, Angelucci C, Athanasopoulos V, Rui L, Hill KM, Yu D, Domaschenz H, Whittle B, Lambe T, Roberts IS, Copley RR, Bell JI, Cornall RJ, Goodnow CC. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature. 2005a;435:452–8.CrossRefGoogle Scholar
  14. 14.
    Yu D, Tan AH, Hu X, Athanasopoulos V, Simpson N, Silva DG, Hutloff A, Giles KM, Leedman PJ, Lam KP, Goodnow CC, Vinuesa CG. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature. 2007;450:299–303.CrossRefGoogle Scholar
  15. 15.
    Glasmacher E, Hoefig KP, Vogel KU, Rath N, Du L, Wolf C, Kremmer E, Wang X, Heissmeyer V. Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression. Nat Immunol. 2010;11:725–33.CrossRefGoogle Scholar
  16. 16.
    Arimura Y, Kato H, Dianzani U, Okamoto T, Kamekura S, Buonfiglio D, Miyoshi-Akiyama T, Uchiyama T, Yagi J. A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in T(h) cells and regulates their responses. Int Immunol. 2002;14:555–66.CrossRefGoogle Scholar
  17. 17.
    Herman AE, Freeman GJ, Mathis D, Benoist C. CD4+CD25+ T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion. J Exp Med. 2004;199:1479–89.CrossRefGoogle Scholar
  18. 18.
    Salomon B, Lenschow DJ, Rhee L, Ashourian N, Singh B, Sharpe A, Bluestone JA. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity. 2000;12:431–40.CrossRefGoogle Scholar
  19. 19.
    Bossaller L, Burger J, Draeger R, Grimbacher B, Knoth R, Plebani A, Durandy A, Baumann U, Schlesier M, Welcher AA, Peter HH, Warnatz K. ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells. J Immunol. 2006;177:4927–32.CrossRefGoogle Scholar
  20. 20.
    Kim CH, Rott LS, Clark-Lewis I, Campbell DJ, Wu L, Butcher EC. Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. J Exp Med. 2001;193:1373–81.CrossRefGoogle Scholar
  21. 21.
    Vinuesa CG, Tangye SG, Moser B, Mackay CR. Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol. 2005b;5:853–65.CrossRefGoogle Scholar
  22. 22.
    Witsch EJ, Peiser M, Hutloff A, Büchner K, Dorner BG, Jonuleit H, Mages HW, Kroczek RA. ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells. Eur J Immunol. 2002;32:2680–6.CrossRefGoogle Scholar
  23. 23.
    Bauquet AT, Jin H, Paterson AM, Mitsdoerffer M, Ho IC, Sharpe AH, Kuchroo VK. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol. 2009;10:167–75.CrossRefGoogle Scholar
  24. 24.
    Ozaki K, Spolski R, Ettinger R, Kim HP, Wang G, Qi CF, Hwu P, Shaffer DJ, Akilesh S, Roopenian DC, Morse HC 3rd, Lipsky PE, Leonard WJ. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol. 2004;173:5361–71.CrossRefGoogle Scholar
  25. 25.
    Shin C, Han JA, Koh H, Choi B, Cho Y, Jeong H, Ra JS, Sung PS, Shin EC, Ryu S, Do Y. CD8α(−) dendritic cells induce antigen-specific T follicular helper cells generating efficient humoral immune responses. Cell Rep. 2015;11:1929–40.CrossRefGoogle Scholar
  26. 26.
    Choi YS, Kageyama R, Eto D, Escobar TC, Johnston RJ, Monticelli L, Lao C, Crotty S. ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity. 2011;34:932–46.CrossRefGoogle Scholar
  27. 27.
    Pedros C, Zhang Y, Hu JK, Choi YS, Canonigo-Balancio AJ, Yates JR 3rd, Altman A, Crotty S, Kong KF. A TRAF-like motif of the inducible costimulator ICOS controls development of germinal center TFH cells via the kinase TBK1. Nat Immunol. 2016;17:825–33.CrossRefGoogle Scholar
  28. 28.
    Stone EL, Pepper M, Katayama CD, Kerdiles YM, Lai CY, Emslie E, Lin YC, Yang E, Goldrath AW, Li MO, Cantrell DA, Hedrick SM. ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation. Immunity. 2015;42:239–51.CrossRefGoogle Scholar
  29. 29.
    Weber JP, Fuhrmann F, Feist RK, Lahmann A, Al Baz MS, Gentz LJ, Vu Van D, Mages HW, Haftmann C, Riedel R, Grün JR, Schuh W, Kroczek RA, Radbruch A, Mashreghi MF, Hutloff A. ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2. J Exp Med. 2015;212:217–33.CrossRefGoogle Scholar
  30. 30.
    Leavenworth JW, Verbinnen B, Yin J, Huang H, Cantor H. A p85α-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells. Nat Immunol. 2015;16:96–106.CrossRefGoogle Scholar
  31. 31.
    Schepp J, Chou J, Skrabl-Baumgartner A, Arkwright PD, Engelhardt KR, Hambleton S, Morio T, Röther E, Warnatz K, Geha R, Grimbacher B. 14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency. Front Immunol. 2017;8:964.CrossRefGoogle Scholar
  32. 32.
    Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Dräger R, Eibel H, Fischer B, Schäffer AA, Mages HW, Kroczek RA, Peter HH. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol. 2003;4:261–8.CrossRefGoogle Scholar
  33. 33.
    Salzer U, Maul-Pavicic A, Cunningham-Rundles C, Urschel S, Belohradsky BH, Litzman J, Holm A, Franco JL, Plebani A, Hammarstrom L, Skrabl A, Schwinger W, Grimbacher B. ICOS deficiency in patients with common variable immunodeficiency. Clin Immunol. 2004;113:234–40.CrossRefGoogle Scholar
  34. 34.
    Chou J, Massaad MJ, Cangemi B, Bainter W, Platt C, Badran YR, Raphael BP, Kamin DS, Goldsmith JD, Pai SY, Al-Herz W, Geha RS. A novel mutation in ICOS presenting as hypogammaglobulinemia with susceptibility to opportunistic pathogens. J Allergy Clin Immunol. 2015;136:794–797.e1.CrossRefGoogle Scholar
  35. 35.
    Takahashi N, Matsumoto K, Saito H, Nanki T, Miyasaka N, Kobata T, Azuma M, Lee SK, Mizutani S, Morio T. Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. J Immunol. 2009;182:5515–27.CrossRefGoogle Scholar
  36. 36.
    Robertson N, Engelhardt KR, Morgan NV, Barge D, Cant AJ, Hughes SM, Abinun M, Xu Y, Koref MS, Arkwright PD, Hambleton S. Astute clinician report: a novel 10 bp frameshift deletion in exon 2 of ICOS causes a combined immunodeficiency associated with an enteritis and hepatitis. J Clin Immunol. 2015;35:598–603.CrossRefGoogle Scholar
  37. 37.
    Warnatz K, Bossaller L, Salzer U, Skrabl-Baumgartner A, Schwinger W, van der Burg M, van Dongen JJ, Orlowska-Volk M, Knoth R, Durandy A, Draeger R, Schlesier M, Peter HH, Grimbacher B. Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency. Blood. 2006;107:3045–52.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of Rheumatology and Clinical ImmunologyMedical Center—University of FreiburgFreiburg im BreisgauGermany
  2. 2.Faculty of Medicine, Center for Chronic Immunodeficiency (CCI)Medical Center—University of FreiburgFreiburg im BreisgauGermany

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