99
Views
17
CrossRef citations to date
0
Altmetric
Original Article

CTLA-4 (CD152) and its involvement in autoimmune disease

, , &
Pages 225-233 | Published online: 07 Jul 2009

REFERENCES

  • Fischer A. Human primary immunodeficiency diseases: A perspective. Nat Immunol 2004; 5: 23-30.
  • Vyse TJ, Todd JA. Genetic analysis of autoimmune disease. Cell 1996; 85: 311-318.
  • Wandstrat A, Wakeland E. The genetics of complex autoimmune diseases: Non-MHC susceptibility genes. Nat Immunol 2001; 2: 802-809.
  • Rose NR, Mackay IR The autoimmune diseases. 3rd ed. San Diego, CA, USA: Academic Press; 1998.
  • Nistico L, Buzzetti R, Pritchard LE, Van der Auwera B, Giovannini C, Bosi E, Larrad MT, Rios MS, Chow CC, Cockram CS, Jacobs K, Mijovic C, Bain SC, Barnett AH, Vandewalle CL, Schuit F, Gorus FK, Tosi R, Pozzilli P, Todd JA. The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry. Hum Mol Genet 1996; 5: 1075-1080.
  • Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdottir H, Grondal G, Bolstad Al, Svenungsson E, Lundberg I, Sturfelt G, Jonssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcon-Segovia D, Steinsson K, Alarcon-Riquelme ME. A regulatory poly-morphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 2002; 32: 666-669.
  • Khoury SJ, Sayegh MH. The roles of the new negative T cell costimulatory pathways in regulating autoimmunity. Immu-nity 2004; 20: 529-538.
  • Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE, Reed PW, Gough SC, Jenkins SC, Palmer SM, et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 1994; 371: 130-136.
  • Hashimoto L, Habita C, Beressi JP, Delepine M, Besse C, Cambon-Thomsen A, Deschamps I, Rotter JI, Djoulah S, James MR, et al. Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome 11q. Nature 1994; 371: 161-164.
  • Rowe RE, Wapelhorst B, Bell GI, Risch N, Spielman RS, Concannon P. Linkage and association between insulin-dependent diabetes mellitus (IDDM) susceptibility and markers near the glucokinase gene on chromosome 7. Nat Genet 1995; 10: 240-242.
  • Ebers GC, Kukay K, Bulman DE, Sadovnick AD, Rice G, Anderson C, Armstrong H, Cousin K, Bell RB, Hader W, Paty DW, Hashimoto S, Oger J, Duquette P, Warren S, Gray T, O'Connor P, Nath A, Auty A, Metz L, Francis G, Paulseth JE, Murray TJ, Pryse-Phillips W, Risch N, et al. A full genome search in multiple sclerosis. Nat Genet 1996; 13: 472-476.
  • Luo DF, Buzzetti R, Rotter JI, Maclaren NK, Raffel Nistico L, Giovannini C, Pozzilli P, Thomson G, She JX. Confirmation of three susceptibility genes to insulin-dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8. Hum Mol Genet 1996; 5: 693-698.
  • Gaffney PM, Kearns GM, Shark KB, Ortmann WA, Selby SA, Malmgren ML, Rohlf KE, Ockenden TC, Messner RP, King RA, Rich SS, Behrens TW. A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families. Proc Natl Acad Sci USA 1998; 95: 14875-14879.
  • Mein CA, Esposito L, Dunn MG, Johnson GC, Timms AE, Goy JV, Smith AN, Sebag-Montefiore L, Merriman ME, Wilson AJ, Pritchard LE, Cucca F, Barnett AH, Bain SC, Todd JA. A search for type 1 diabetes susceptibility genes in families from the United Kingdom. Nat Genet 1998; 19: 297-300.
  • Moser KL, Neas BR, Salmon JE, Yu H, Gray-McGuire C, Asundi N, Bruner GR, Fox J, Kelly J, Henshall S, Bacino D, Dietz M, Hogue R, Koelsch G, Nightingale L, Shaver T, Abdou NI, Albert DA, Carson C, Petri M, Treadwell EL, James JA, Harley JB. Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1 q in African-American pedigrees. Proc Natl Acad Sci USA 1998; 95: 14869-14874.
  • Shai R, Quismorio Jr, FP, Li L, Kwon OJ, Morrison J, Wallace DJ, Neuwelt CM, Brautbar C, Gauderman WJ, Jacob CO. Genome-wide screen for systemic lupus erythe-matosus susceptibility genes in multiplex families. Hum Mol Genet 1999; 8: 639-644.
  • Eaves IA, Merriman TR, Barber RA, Nutland S, Tuomilehto-Wolf E, Tuomilehto J, Cucca F, Todd JA. The genetically isolated populations of Finland and sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes. Nat Genet 2000; 25: 320-323.
  • Lindqvist AK, Steinsson K, Johanneson B, Kristjansdottir H, Arnasson A, Grondal G, Jonasson I, Magnusson V, Sturfelt G, Truedsson L, Svenungsson E, Lundberg I, Terwilliger JD, Gyllensten UB, Alarcon-Riquelme ME. A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. J Autoimmun 2000; 14: 169-178.
  • Hakonarson H, Bjornsdottir US, Halapi E, Palsson S, Adalsteinsdottir E, Gislason D, Finnbogason G, Gislason T, Kristjansson K, Arnason T, Birkisson I, Frigge ML, Kong A, Gulcher JR, Stefansson K. A major susceptibility gene for asthma maps to chromosome 14q24. Am J Hum Genet 2002; 71: 483-491.
  • Saarela J, Schoenberg Fejzo M, Chen D, Finnila S, Parkkonen M, Kuokkanen S, Sobel E, Tienari PJ, Sumelahti ML, Wikstrom J, Elovaara I, Koivisto K, Pirttila T, Reunanen M, Palotie A, Peltonen L. Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24. Hum Mol Genet 2002; 11: 2257-2267.
  • Ghosh S, Palmer SM, Rodrigues NR, Cordell HJ, Hearne CM, Coma11 RJ, Prins JB, McShane P, Lathrop GM, Peterson LB, et al. Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nat Genet 1993; 4: 404-409.
  • Drake CG, Babcock SK, Palmer E, Kotzin BL. Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice. Proc Natl Acad Sci USA 1994; 91: 4062-4066.
  • Garchon HJ, Luan JJ, Eloy L, Bedossa P, Bach JF. Genetic analysis of immune dysfunction in non-obese diabetic (NOD) mice: Mapping of a susceptibility locus close to the Bc1-2 gene correlates with increased resistance of NOD T cells to apoptosis induction. Eur J Immunol 1994; 24: 380-384.
  • Penha-Goncalves C, Leijon K, Persson L, Holmberg D. Type 1 diabetes and the control of dexamethazone-induced apoptosis in mice maps to the same region on chromosome 6. Genomics 1995; 28: 398-404.
  • Sundvall M, Jirholt J, Yang HT, jansson L, Engstrom A, Pettersson U, Holmdahl R. Identification of murine loci associated with susceptibility to chronic experimental auto-immune encephalomyelitis. Nat Genet 1995; 10: 313-317.
  • Encinas JA, Weiner HL, Kuchroo VK. Inheritance of susceptibility to experimental autoimmune encephalomyelitis. J Neurosci Res 1996; 45: 655-669.
  • Wu J, Longmate JA, Adamus G, Hargrave PA, Wakeland EK. Interval mapping of quantitative trait loci controlling humoral immunity to exogenous antigens: Evidence that non-MHC immune response genes may also influence susceptibility to autoimmunity. J Immunol 1996; 157: 2498-2505.
  • Colucci F, Bergman ML, Penha-Goncalves C, Cilio CM, Holmberg D. Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to the Idd5 diabetes susce-ptibility region. Proc Natl Acad Sci USA 1997; 94: 8670-8674.
  • Griffiths MM, Encinas JA, Remmers EF, Kuchroo VK, Wilder RL. Mapping autoimmunity genes. Curr Opin Immunol 1999; 11: 689-700.
  • Bell GI, Horita S, Karam JH. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes 1984; 33: 176-183.
  • Bennett ST, Wilson AJ, Esposito L, Bouzekri N, Undlien DE, Cucca F, Nistico L, Buzzetti R, Bosi E, Pociot F, Nerup J, Cambon-Thomsen A, Pugliese A, Shield JP, McKinney PA, Bain SC, Polychronakos C, Todd JA. Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group. Nat Genet 1997; 17: 350-352.
  • Walport MJ, Davies KA, Botto M. Cl q and systemic lupus erythematosus. Immunobiology 1998; 199: 265-285.
  • Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001; 411: 599-603.
  • Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001; 411: 603-606.
  • Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, Rainbow DB, Hunter KM, Smith AN, Di Genova G, Herr MH, Dahlman I, Payne F, Smyth D, Lowe C, Twells RC, Howlett S, Healy B, Nutland S, Rance HE, Everett V, Smink LJ, Lam AC, Cordell HJ, Walker NM, Bordin C, Hulme J, Motzo C, Cucca F, Hess JF, Metzker ML, Rogers J, Gregory S, Allahabadia A, Nithiyananthan R, Tuomilehto-Wolf E, Tuomilehto J, Bingley P, Gillespie KM, Undlien DE, Ronningen KS, Guja C, Ionescu-Tirgoviste C, Savage DA, Maxwell AP, Carson DJ, Patterson CC, Franklyn JA, Clayton DG, Peterson LB, Wicker LS, Todd JA, Gough SC. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423: 506-511.
  • Wicker LS, Todd JA, Prins JB, Podolin PL, Renjilian RJ, Peterson LB. Resistance alleles at two non-major histo-compatibility complex-linked insulin-dependent diabetes loci on chromosome 3, Idd3 and Iddl 0, protect nonobese diabetic mice from diabetes. J Exp Med 1994; 180: 1705-1713.
  • Wicker LS, Todd JA, Peterson LB. Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol 1995; 13: 179-200.
  • Morel L, Yu Y, Blenman KR, Caldwell RA, Wakeland EK. Production of congenic mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain. Mamm Genome 1996; 7: 335-339.
  • Podolin PL, Denny P, Lord CJ, Hill NJ, Todd JA, Peterson LB, Wicker LS, Lyons PA. Congenic mapping of the insulin-dependent diabetes (Idd) gene, Iddl 0, localizes two genes mediating the Iddl 0 effect and eliminates the candidate Fcgrl. J Immunol 1997; 159: 1835-1843.
  • Rogner UC, Boitard C, Morin J, Melanitou E, Avner P. Three loci on mouse chromosome 6 influence onset and final incidence of type I diabetes in NOD.C3H congenic strains. Genomics 2001; 74: 163-171.
  • Lamhamedi-Cherradi SE, Boulard O, Gonzalez C, Kassis N, Damotte D, Eloy L, Fluteau G, Levi-Strauss M, Garchon HJ. Further mapping of the Idd5.1 locus for autoimmune diabetes in NOD mice. Diabetes 2001; 50: 2874-2878.
  • Bergman ML, Duarte N, Campino S, Lundholm M, Motta V, Lejon K, Penha-Goncalves C, Holmberg D. Diabetes protection and restoration of thymocyte apoptosis in NOD Idd6 congenic strains. Diabetes 2003; 52: 1677-1682.
  • Podolin PL, Wilusz MB, Cubbon RM, Pajvani U, Lord CJ, Todd JA, Peterson LB, Wicker LS, Lyons PA. Differential glycosylation of interleukin 2, the molecular basis for the NOD Idd3 type 1 diabetes gene? Cytokine 2000; 12: 477-482.
  • Vijayakrishnan L, Slavik JM, Illes Z, Greenwald RJ, Rainbow D, Greve B, Peterson LB, Hafler DA, Freeman GJ, Sharpe AH, Wicker LS, Kuchroo VK. An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity 2004; 20: 563-575.
  • Vaidya B, Pearce S. The emerging role of the CTLA-4 gene in autoimmune endocrinopathies. Eur J Endocrinol 2004; 150: 619-626.
  • Cornall RJ, Prins JB, Todd JA, Pressey A, DeLarato NH, Wicker LS, Peterson LB. Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1. Nature 1991; 353: 262-265.
  • Garchon HJ, Bedossa P, Eloy L, Bach JF. Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice. Nature 1991; 353: 260-262.
  • Marron MP, Raffel LJ, Garchon HJ, Jacob CO, Serrano-Rios M, Martinez Larrad MT, Teng WP, Park Y, Zhang ZX, Goldstein DR, Tao YW, Beaurain G, Bach JF, Huang HS, Luo DF, Zeidler A, Rotter JI, Yang MC, Modilevsky T, Maclaren NK, She JX. Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. Hum Mol Genet 1997; 6: 1275-1282.
  • Donner H, Braun J, Seidl C, Rau H, Finke R, Ventz M, Walfish PG, Usadel KH, Badenhoop K. Codon 17 polymorphism of the cytotoxic T lymphocyte antigen 4 gene in Hashimoto's thyroiditis and Addison's disease. J Chin Endocrinol Metab 1997; 82: 4130-4132.
  • Esposito L, Hill NJ, Pritchard LE, Cucca F, Muxworthy C, Merriman ME, Wilson A, Julier C, Delepine M, Tuomilehto J, Tuomilehto-Wolf E, Ionesco-Tirgoviste C, Nistico L, Buzzetti R, Pozzilli P, Ferrari M, Bosi E, Pociot F, Nerup J, Bain SC, Todd JA. Genetic analysis of chromosome 2 in type 1 diabetes: Analysis of putative loci IDDM7, IDDM12, and IDDM13 and candidate genes NRA/VIP1 and IA-2 and the interleukin-1 gene cluster. IMDIAB Group. Diabetes 1998; 47: 1797-1799.
  • Kemp EH, Ajjan RA, Husebye ES, Peterson P, Uibo R, Imrie H, Pearce SH, Watson PF, Weetman AP. A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is associated with autoimmune Addison's disease in English patients. Chin Endocrinol (Oxf) 1998; 49: 609-613.
  • Vaidya B, Imrie H, Perros P, Young ET, Kelly WE, Carr D, Large DM, Toft AD, McCarthy MI, Kendall-Taylor P, Pearce SH. The cytotoxic T lymphocyte antigen-4 is a major Graves' disease locus. Hum Mol Genet 1999; 8: 1195-1199.
  • Marron MP, Zeidler A, Raffel LJ, Eckenrode SE, Yang JJ, Hopkins DI, Garchon HJ, Jacob CO, Serrano-Rios M, Martinez Larrad MT, Park Y, Bach JF, Rotter JI, Yang MC, She JX. Genetic and physical mapping of a type 1 diabetes susceptibility gene (IDDM12) to a 100-kb phagemid artificial chromosome clone containing D2572-CTLA4-D25105 on chromosome 2q33. Diabetes 2000; 49: 492-499.
  • Djilali-Saiah I, Schmitz J, Harfouch-Hammoud E, Mougenot JF, Bach JF, Caillat-Zucman S. CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. Gut 1998; 43: 187-189.
  • Pullmann Jr., R, Lukac J, Skerenova M, Rovensky J, Hybenova J, Melus V, Celec S, Pullmann R, Hyrdel R. Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus. Chin Exp Rheumatol 1999; 17: 725-729.
  • Ahmed S, Ihara K, Kanemitsu S, Nakashima H, Otsuka T, Tsuzaka K, Takeuchi T, Hara T. Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. Rheumatology (Oxford) 2001; 40: 662-667.
  • Aguilar F, Torres B, Sanchez-Roman J, Nunez-Roldan A, Gonzalez-Escribano MF. CTLA4 polymorphism in Spanish patients with systemic lupus erythematosus. Hum Immunol 2003; 64: 936-940.
  • Barreto M, Santos E, Ferreira R, Fesel C, Fontes MF, Pereira C, Martins B, Andreia R, Viana JF, Crespo F, Vasconcelos C, Ferreira C, Vicente AM. Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. Eur J Hum Genet 2004; 12: 620-626.
  • Harbo HF, Celius EG, Vartdal F, Spurkland A. CTLA4 promoter and exon 1 dimorphisms in multiple sclerosis. Tissue Antigens 1999; 53: 106-110.
  • Agarwal K, Jones DE, Daly AK, James OF, Vaidya B, Pearce S, Bassendine ME CTLA-4 gene polymorphism confers susceptibility to primary biliary cirrhosis. J Hepatol 2000; 32: 538-541.
  • Seidl C, Donner H, Fischer B, Usadel KH, Seifried E, Kaltwasser JP, Badenhoop K. CTLA4 codon 17 dimorphism in patients with rheumatoid arthritis. Tissue Antigens 1998; 51: 62-66.
  • Polymeropoulos MH, Xiao H, Rath DS, Merril CR. Dinucleotide repeat polymorphism at the human CTLA4 gene. Nucleic Acids Res 1991; 19: 4018.
  • Deichmann K, Heinzmann A, Bruggenolte E, Forster J, Kuehr J. An Mse I RFLP in the human CTLA4 promotor. Biochem Biophys Res Commun 1996; 225: 817-818.
  • Magistrelli G, Jeannin P, Herbault N, Benoit De Coignac A, Gauchat JF, Bonnefoy JY, Delneste Y. A soluble form of CTLA-4 generated by alternative splicing is expressed by nonstimulated human T cells. Eur J Immunol 1999; 29: 3596-3602.
  • Oaks MK, Hallett KM. Cutting edge: A soluble form of CTLA-4 in patients with autoimmune thyroid disease. J Immunol 2000; 164: 5015-5018.
  • Hill NJ, Lyons PA, Armitage N, Todd JA, Wicker LS, Peterson LB. NOD Idd5 locus controls insulitis and diabetes and overlaps the orthologous CTLA4/IDDM12 and NRAMP1 loci in humans. Diabetes 2000; 49: 1744-1747.
  • Wicker LS, Chamberlain G, Hunter K, Rainbow D, Howlett S, Tiffen P, Clark J, Gonzalez-Munoz A, Cumiskey AM, Rosa RL, Howson JM, Smink U, Kingsnorth A, Lyons PA, Gregory S, Rogers J, Todd JA, Peterson LB. Fine mapping, gene content, comparative sequencing, and expression analyses support Ctla4 and Nrampl as candidates for Idd5.1 and Idd5.2 in the nonobese diabetic mouse. J Immunol 2004; 173: 164-173.
  • Greve B, Vijayakrishnan L, Kubal A, Sobel RA, Peterson LB, Wicker LS, Kuchroo VK. The diabetes susceptibility locus Idd5.1 on mouse chromosome 1 regulates ICOS expression and modulates murine experimental autoimmune encephalo-myelitis. J Immunol 2004; 173: 157-163.
  • Davis MM, Bjorkman PJ. T-cell antigen receptor genes and T-cell recognition. Nature 1988; 334: 395-402.
  • Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol 2001; 1: 220-228.
  • Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell cosfimulation. Annu Rev Immunol 1996; 14: 233-258.
  • Thompson CB, Lindsten T, Ledbetter JA, Kunkel SL, Young HA, Emerson SG, Leiden JM, June CH. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci USA 1989; 86: 1333-1337.
  • Lindsten T, June CH, Ledbetter JA, Stella G, Thompson CB. Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science 1989; 244: 339-343.
  • Boise LH, Minn AJ, Noel PJ, June CH, Accavitti MA, Lindsten T, Thompson CB. CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL. Immunity 1995; 3: 87-98.
  • Linsley PS, Brady W, Grosmaire L, Aruffo A, Damle NK, Ledbetter JA. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J Exp Med 1991; 173: 721-730.
  • Linsley PS, Ledbetter JA. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol 1993; 11: 191-212.
  • Linsley PS, Greene JL, Tan P, Bradshaw J, Ledbetter JA, Anasetti C, Damle NK. Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J Exp Med 1992; 176: 1595-1604.
  • Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, Thompson CB, Bluestone JA. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1994; 1: 405-413.
  • Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995; 182: 459-465.
  • Schneider H, Martin M, Agarraberes FA, Yin L, Rapoport I, Kirchhausen T, Rudd CE. Cytolytic T lymphocyte-associ-ated antigen-4 and the TCR zeta/CD3 complex, but not CD28, interact with clathrin adaptor complexes AP-1 and AP-2. J Immunol 1999; 163: 1868-1879.
  • 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: 535-543.
  • Egen JG, Allison JP. Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity 2002; 16: 23-35.
  • Sansom DM, Manzotti CN, Zheng Y. What's the difference between CD80 and CD86? Trends Immunol 2003; 24: 314-319.
  • Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1994; 1: 793-801.
  • Larsen CP, Ritchie SC, Hendrix R, Linsley PS, Hathcock KS, Hodes RJ, Lowry RP, Pearson TC. Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells. J Immunol 1994; 152: 5208-5219.
  • Ikemizu S, Gilbert RJ, Fennelly JA, Collins AV, Harlos K, Jones EY, Stuart DI, Davis SJ. Structure and dimerization of a soluble form of B7-1. Immunity 2000; 12: 51-60.
  • Collins AV, Brodie DW, Gilbert RJ, Iaboni A, Manso-Sancho R, Walse B, Stuart DI, van der Merwe PA, Davis SJ. The interaction properties of costimulatory molecules revisited. Immunity 2002; 17: 201-210.
  • Thompson CB, Allison JP. The emerging role of CTLA-4 as an immune attenuator. Immunity 1997; 7: 445-450.
  • Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995; 270: 985-988.
  • Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995; 3: 541-547.
  • Calvo CR, Amsen D, Kruisbeek AM. Cytotoxic T lymphocyte antigen 4 (CTLA-4) interferes with extracellular signal-regulated kinase (ERK) and Jun NH2-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor zeta and ZAP70. J Exp Med 1997; 186: 1645-1653.
  • Olsson C, Riesbeck K, Dohlsten M, Michaelsson E, Riebeck K. CTLA-4 ligation suppresses CD28-induced NF-kappaB and AP-1 activity in mouse T cell blasts. J Biol Chem 1999; 274: 14400-14405.
  • Lee KNI, Chuang E, Griffin M, Khattri R, Hong DK, Zhang W, Straus D, Samelson LE, Thompson CB, Bluestone JA. Molecular basis of T cell inactivation by CTLA-4. Science 1998; 282: 2263-2266.
  • Chikuma S, Bluestone JA. CTLA-4: Acting at the Synapse. Mol Intervent 2002; 2: 205-208.
  • Hosken NA, Shibuya K, Heath AW, Murphy KNI, O'Garra A. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model. J Exp Med 1995; 182: 1579-1584.
  • Lenschow DJ, Herold KC, Rhee L, Patel B, Koons A, Qin HY, Fuchs E, Singh B, Thompson CB, Bluestone JA. CD28/B7 regulation of Thl and Th2 subsets in the development of autoimmune diabetes. Immunity 1996; 5: 285-293.
  • Rulifson IC, Sperling Al, Fields PE, Fitch FW, Bluestone JA. CD28 costimulation promotes the production of Th2 cytokines. J Immunol 1997; 158: 658-665.
  • Oosterwegel MA, Greenwald RJ, Mandelbrot DA, Lorsbach RB, Sharpe AH. CTLA-4 and T cell activation. Curr Opin Immunol 1999; 11: 294-300.
  • Khattri R, Auger JA, Griffin MD, Sharpe AH, Bluestone JA. Lymphoproliferative disorder in CTLA-4 knockout mice is characterized by CD28-regulated activation of Th2 responses. J Immunol 1999; 162: 5784-5791.
  • Kato T, Nariuchi H. Polarization of naive CD4+ T cells toward the Thl subset by CTLA-4 costimulation. J Immunol 2000; 164: 3554-3562.
  • Schweitzer AN, Borriello F, Wong RC, Abbas AK, Sharpe AH. Role of costimulators in T cell differentiation: Studies using antigen-presenting cells lacking expression of CD80 or CD86. J Immunol 1997; 158: 2713-2722.
  • Schweitzer AN, Sharpe AH. Studies using antigen-presenting cells lacking expression of both B7-1 (CD80) and B7-2 (CD86) show distinct requirements for B7 molecules during priming versus restimulation of Th2 but not Thl cytokine production. J Immunol 1998; 161: 2762-2771.
  • McAdam AJ, Schweitzer AN, Sharpe AH. The role of B7 co-stimulation in activation and differentiation of CD4+ and CD8+ T cells. Immunol Rev 1998; 165: 231-247.
  • Bour-Jordan H, Grogan JL, Tang Q, Auger JA, Locksley RM, Bluestone JA. CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage commitment. Nat Immunol 2003; 4: 182-188.
  • Bachmann MF, Waterhouse P, Speiser DE, McKall-Faienza K, Mak TW, Ohashi PS. Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. J Immunol 1998; 160: 95-100.
  • Bachmann MF, Kohler G, Ecabert B, Mak TW, Kopf M. Cutting edge: Llymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous. J Immunol 1999; 163: 1128-1131.
  • Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 2000; 192: 295-302.
  • Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000; 192: 303-310.
  • Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 1992; 359: 693-699.
  • Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 1993; 90: 770-774.
  • Chen W, Jin W, Wahl SM. Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces trans-forming growth factor beta (TGF-beta) production by murine CD4(+) T cells. J Exp Med 1998; 188: 1849-1857.
  • Gomes NA, Gattass CR, Barreto-De-Souza V, Wilson ME, DosReis GA. TGF-beta mediates CTLA-4 suppression of cellular immunity in murine kalaazar. J Immunol 2000; 164: 2001-2008.
  • Kitani A, Chua K, Nakamura K, Strober W. Activated self-MHC-reactive T cells have the cytokine phenotype of Th3/T regulatory cell 1 T cells. J Immunol 2000; 165: 691-702.
  • Sullivan TJ, Letterio JJ, van Elsas A, Mamura M, van Amelsfort J, Sharpe S, Metzler B, Chambers CA, Allison JP. Lack of a role for transforming growth factor-beta in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activation. Proc Natl Acad Sci USA 2001; 98: 2587-2592.
  • Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003; 4: 1206-1212.
  • Grohmann U, Orabona C, Fallarino F, Vacca C, Calcinaro F, Falorni A, Candeloro P, Belladonna ML, Bianchi R, Fioretti MC, Puccetti P. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol 2002; 3: 1097-1101.
  • Lenschow DJ, Ho SC, Sattar H, Rhee L, Gray G, Nabavi N, Herold KC, Bluestone JA. Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J Exp Med 1995; 181: 1145-1155.
  • Finck BK, Linsley PS, Wofsy D. Treatment of murine lupus with CTLA4Ig. Science 1994; 265: 1225-1227.
  • Khoury SJ, Akalin E, Chandraker A, Turka LA, Linsley PS, Sayegh MH, Hancock WW. CD28-B7 costimulatory block-ade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyelitis and inhibits Thl but spares Th2 cytokines in the central nervous system. J Immunol 1995; 155: 4521-4524.
  • Knoerzer DB, Karr RW, Schwartz BD, Mengle-Gaw U. Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig. J Chin Invest 1995; 96: 987-993.
  • Webb LM, Walmsley MJ, Feldmann M. Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 co-stimulatory pathway: requirement for both B7-1 and B7-2. Eur J Immunol 1996; 26: 2320-2328.
  • Perrin PJ, Maldonado JH, Davis TA, June CH, Racke MK. CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis. J Immunol 1996; 157: 1333-1336.
  • Karandikar NJ, Vanderlugt CL, Walunas TL, Miller SD, Bluestone JA. CTLA-4: a negative regulator of autoimmune disease. J Exp Med 1996; 184: 783-788.
  • Daikh DI, Finck BK, Linsley PS, Hollenbaugh D, Wofsy D. Long-term inhibition of murine lupus by brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways. J Immunol 1997; 159: 3104-3108.
  • Luhder F, Hoglund P, Allison JP, Benoist C, Mathis D. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates the unfolding of autoimmune diabetes. J Exp Med 1998; 187: 427-432.
  • 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: 431-440.
  • Tang Q, Henriksen KJ, Boden EK, Tooley AJ, Ye J, Subudhi SK, Zheng XX, Strom TB, Bluestone JA. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 2003; 171: 3348-3352.
  • Bluestone JA. Is CTLA-4 a master switch for peripheral T cell tolerance? J Immunol 1997; 158: 1989-1993.
  • Brunet JF, Denizot F, LucianiMF, Roux-Dosseto M, Suzan M, Mattei MG, Golstein P. A new member of the immunoglobulin superfamily—CTLA-4. Nature 1987; 328: 267-270.
  • Wagner Jr., DH, Hagman J, Linsley PS, Hodsdon W, Freed JH, Newell MK. Rescue of thymocytes from glucocorticoid-induced cell death mediated by CD28/CTLA-4 costimulatory interactions with B7-1/B7-2. JExp Med 1996; 184: 1631-1638.
  • Cilio CM, Daws MR, Malashicheva A, Sentman CL, Holmberg D. Cytotoxic T lymphocyte antigen 4 is induced in the thymus upon in vivo activation and its blockade prevents anti-CD3-mediated depletion of thymocytes. J Exp Med 1998; 188: 1239-1246.
  • Nelson AJ, Hosier S, Brady W, Linsley PS, Farr AG. Medullary thymic epithelium expresses a ligand for CTLA4 in situ and in vitro. J Immunol 1993; 151: 2453-2461.
  • Degermann S, Surh CD, Glimcher LH, Sprent J, Lo D. B7 expression on thymic medullary epithelium correlates with epithelium-mediated deletion of V beta 5+ thymocytes. J Immunol 1994; 152: 3254-3263.
  • Waterhouse P, Bachmann MF, Penninger JM, Ohashi PS, Mak TW. Normal thymic selection, normal viability and decreased lymphoproliferation in T cell receptor-transgenic CTLA-4-deficient mice. Eur J Immunol 1997; 27: 1887-1892.
  • Chambers CA, Cado D, Truong T, Allison JP. Thymocyte development is normal in CTLA-4-deficient mice. Proc Natl Acad Sci USA 1997; 94: 9296-9301.
  • Buhlmann JE, Elkin SK, Sharpe AH. A role for the B7-1/B7-2: CD28/CTLA-4 pathway during negative selection. J Immunol 2003; 170: 5421-5428.
  • Modigliani Y, Thomas-Vaslin V, Bandeira A, Coltey M, Le Douarin NM, Coutinho A, Salaun J. Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype. Proc Natl Acad Sci USA 1995; 92: 7555-7559.
  • Modigliani Y, Coutinho A, Pereira P, Le Douarin N, Thomas-Vaslin V, Burlen-Defranoux O, Salaun J, Bandeira A. Establishment of tissue-specific tolerance is driven by regulatory T cells selected by thymic epithelium. Eur J Immunol 1996; 26: 1807-1815.
  • Coyle AJ, Gutierrez-Ramos JC. The expanding B7 super-family: increasing complexity in costimulatory signals regulating T cell function. Nat Immunol 2001; 2: 203-209.
  • 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.
  • Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol 2002; 2: 116-126.
  • Rothstein DM, Sayegh MH. T-cell costimulatory pathways in allograft rejection and tolerance. Immunol Rev 2003; 196: 85-108.
  • Carreno BM, Collins M. BTLA: A new inhibitory receptor with a B7-like ligand. Trends Immunol 2003; 24: 524-527.
  • Kroczek RA, Mages HW, Hutloff A. Emerging paradigms of T-cell co-stimulation. Curr Opin Immunol 2004; 16: 321-327.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.