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CTLA-4

  • Reference work entry
  • First Online:
Encyclopedia of Medical Immunology

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Synonyms

APC- antigen presenting cell; ARF- ADP-ribosylation factor; CD- clusters of differentiation; cdk- cyclin-dependent kinases; CTLA- 4 – cytotoxicT lymphocyte antigen 4; ICOS- Inducible T-cell CoStimulator; IDO - indoleamine 2, 3-dioxygenase; ITIM -immunoreceptor tyrosine-based inhibitory motif; LAT- linker of activated T cells; LAX - linker for activation of X cells; LFA-1 – lymphocyte function-associated antigen-1; MHC- major histocompatibility complex; PLD- phospholipase D; PP2A- serine/threonine phosphatase 2A; SIT - SHP2-interacting transmembrane adapter protein; SLE- Systemic Lupus Erythematosus; T reg – regulatory T cell; TCR- T cell antigen receptor; TIRC7- T cell immune response cDNA 7; TLR- Toll-like receptor; TRIM - T-cell receptor interacting molecule; ZAP-70 -Zeta-chain-associated protein kinase 70

Definition

For antigen-induced activation of a T cell to occur, an antigen-presenting cell (APC) must provide the T cell with two signals. The first is the antigen, in the...

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References

  • Davis PM, Nadler SG, Stetsko DK, Suchard SJ. Abatacept modulates human dendritic cell-stimulated T-cell proliferation and effector function independent of IDO induction. Clin Immunol. 2008;126(1):38–47. Epub 2007 Oct 22.

    PubMed  CAS  Google Scholar 

  • Englehardt JJ, Sullivan TJ, Allison JP. CTLA-4 overexpression inhibits T cell responses through CD28-B7-dependent mechanism. J Immunol. 2006;177:1052–61.

    Google Scholar 

  • Friedline RH, Brown DS, Nguyen H, Kornfeld H, Lee J, Zhang Y, Appleby M, Der SD, Kang J, Chambers CA. CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance. J Exp Med. 2009;206(2):421–34. Epub 2009 Feb 2.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hertz CJ, Kiertscher SM, Godowski PJ, Bouis DA, Norgard MV, Roth MD, Modlin RL. Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. J Immunol. 2001;166(4):2444–50.

    PubMed  CAS  Google Scholar 

  • Khan S, Burt DJ, Ralph C, Thistlethwaite FC, Hawkins RE, Elkord E. Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells. Clin Immunol. 2011;138(1):85–96. Epub 2010 Nov 5.

    PubMed  CAS  Google Scholar 

  • Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991;174(3):561–9.

    PubMed  CAS  Google Scholar 

  • Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity. 1996;4(6):535–43.

    PubMed  CAS  Google Scholar 

  • Madrenas J, Chau LA, Teft WA, Wu PW, Jussif J, Kasaian M, Carreno BM, Ling V. Conversion of CTLA-4 from inhibitor to activator of T cells with a bispecific tandem single-chain Fv ligand. J Immunol. 2004;172:5948–56.

    PubMed  CAS  Google Scholar 

  • Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database of Syst Rev. 2009 (4):CD007277. doi:10.1002/14651858.CD007277.pub2.

    Google Scholar 

  • Mease P, Genovese MC, Gladstein G, Kivitz AJ, Ritchlin C, Tak PP, Wollenhaupt J, Bahary O, Becker J-C, Kelly S, Sigal L, Tang J, Gladman D. Abatacept in the treatment of patients with psoriatic arthritis: results of a double-blind, randomized, placebo-controlled phase 2 trial. Arthritis Rheum. 2011;63:939–48.

    PubMed  CAS  Google Scholar 

  • Merrill JT, Burgos-Vargas R, Westhovens R, Chalmers A, D’Cruz D, Wallace DJ, Bae SC, Sigal L, Becker J-C, Kelly S, Raghupathi K, Lit T, Peng Y, Kinaszczuk M, Nash P. The efficacy and safety of abatacept in systemic lupus erythematosus: the results of a 12 month exploratory study. Arthritis Rheum. 2010;62(10):3077–87.

    PubMed  CAS  Google Scholar 

  • Noel PJ, Boise LH, Thompson CB. Regulation of T cell activation by CD28 and CTLA4. Adv Exp Med Biol. 1996;406:209–17.

    PubMed  CAS  Google Scholar 

  • Park KS, Baek JA, Do JE, Bang D, Lee ES. CTLA4 gene polymorphisms and soluble CTLA4 protein in Behcet’s disease. Tissue Antigens. 2009;74(3):222–7. Epub 2009 Jun 25.

    PubMed  CAS  Google Scholar 

  • Rudd CE, Taylor A, Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol Rev. 2009;229(1):12–26.

    PubMed  CAS  Google Scholar 

  • Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Pérez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhães C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Calvo Penades I, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace C, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH, for the Paediatric Rheumatology INternational Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Efficacy and safety of abatacept in children with juvenile idiopathic arthritis: a randomized, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372(9636):383–91.

    PubMed  CAS  Google Scholar 

  • Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Pérez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhães C, Chavez J, Huemer C, Kivitz A, Blanco FJ, Foeldvari I, Hofer M, Horneff G, Huppertz H-I, Job Deslandre C, Loy A, Minden K, Punaro M, Nunez AF, Sigal LH, Block AJ, Nys M, Martini A, Giannini EH, for the Paediatric Rheumatology INternational Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis & Rheum. 2010;62(6):1792–802.

    CAS  Google Scholar 

  • Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, Wei B, Hogg N, Garside P, Rudd CE. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313(29 Sept):1972–5.

    PubMed  CAS  Google Scholar 

  • Sigal LH. Basic science for clinicians 55: CTLA-4. J Clin Rheumatol. 2012;18(3):155–8. doi:10.1097/RHU.0b013e31824ea103.

    PubMed  Google Scholar 

  • Sondak VK, Smalley KS, Kudchadkar R, Grippon S, Kirkpatrick P. Ipilimumab. Nat Rev Drug Discov. 2011;10(6):411–2.

    PubMed  CAS  Google Scholar 

  • Stamper CC, Zhang Y, Tobin JF, Erbe DV, Ikemizu S, Davis SJ, Stahl ML, Seehra J, Somers WS, Mosyak L. Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature. 2001;410(6828):608–11.

    PubMed  CAS  Google Scholar 

  • Tang AL, Teijaro JR, Njau MN, Chandran SS, Azimzadeh A, Nadler SG, Rothstein DM, Farber DL. CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis. J Immunol. 2008;181(3):1806–13.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Vincenti F, Dritselis A, Kirkpatrick P. Belatacept. Nat Rev Drug Discov. 2011;10(9):655–6. doi:10.1038/nrd3536.

    PubMed  CAS  Google Scholar 

  • Wing K, Yamaguchi T, Sakaguchi S. Cell-autonomous and –non-autonomous roles of CTLA-4 in immune regulation. Trends Immunol. 2011;32(9):428–33. doi:10.1016/j.it.2011.06.002.

    PubMed  CAS  Google Scholar 

  • Ying H, Yang L, Qiao G, Li Z, Zhang L, Yin F, Xie D, Zhang J. CTLA-4-B7 interaction suppresses Th17 cell differentiation. J Immunol. 2010;185:1375–8.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Yokosuka T, Kobayashi W, Takamatsu M, Sakata-Sogawa K, Zeng H, Hashimoto-Tane A, Yagita H, Tokunaga M, Saito T. Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation. Immunity. 2010;33(3):326–39.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Departments of Medicine and Pediatrics, Department of Molecular Genetics and Microbiology, UMDNJ–Robert Wood Johnson Medical School, 125 Paterson Street - MEB 484, 8901, New Brunswick, NJ, USA

    Leonard H. Sigal

Authors
  1. Leonard H. Sigal
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Correspondence to Leonard H. Sigal .

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

    Ian R. Mackay

  2. Center for Autoimmune Disease Research, Department of Molecular Microbiology and Immunology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA

    Noel R. Rose

  3. The Feinstein Institute for Medical Research, Manhasset, NY, USA

    Betty Diamond

  4. The Feinstein Institute for Medical Research, Manhasset, NY, USA

    Anne Davidson

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Sigal, L.H. (2014). CTLA-4. In: Mackay, I.R., Rose, N.R., Diamond, B., Davidson, A. (eds) Encyclopedia of Medical Immunology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-84828-0_19

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  • DOI: https://doi.org/10.1007/978-0-387-84828-0_19

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-84827-3

  • Online ISBN: 978-0-387-84828-0

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