Skip to main content
SpringerLink
Log in

The balance of immune responses: costimulation verse coinhibition

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Many of the B7 superfamily members (e.g., B7-1, B7-2, ICOS-L, B7-H1, B7-DC) were initially characterized as T cell costimulatory molecules. However, more recently it has become clear they can also coinhibit T cell responses. We review many of the B7 family members, with a particular focus on B7-H1, and examine their role in autoimmunity, transplant rejection, and cancer pathogenesis. It is crucial to understand that many B7 family members have opposing effects on an immune response. This cautions against using clinical immunotherapeutic reagents targeted against these molecules until we gain a better understanding of the circumstances that regulate the outcomes of the T cell response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CTLA :

Cytotoxic T lymphocyte antigen

EAE :

Experimental autoimmune encephalomyelitis

ICOS :

Inducible costimulator

ICOS-L :

Ligand for inducible costimulator

ITIM :

Immunoreceptor tyrosine-based inhibitory motif

ITSM :

Immunoreceptor tyrosine-based switch motif

mAb :

Monoclonal antibody

SH :

Src homology

SHIP :

SH2-containing inositol phosphatase

SHP :

SH2-containing tyrosine phosphatase

References

  1. Thompson CB, Lindsten T, Ledbetter JA, Kunkel SL, Young HA, Emerson SG, Leiden JM, June JM (1989) CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci U S A 86:1333–1337

    CAS  PubMed  Google Scholar 

  2. Boise LH, Minn AJ, Noel PJ, June CH, Accavitti MA, Lindsten T, Thompson CB (1995) CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL. Immunity 3:87–98

    CAS  PubMed  Google Scholar 

  3. Lenschow DJ, Walunas TL, Bluestone JA (1996) CD28/B7 system of T cell costimulation. Annu Rev Immunol 14:233–258

    CAS  PubMed  Google Scholar 

  4. Salomon B, Bluestone JA (2001) Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 19:225–252

    CAS  PubMed  Google Scholar 

  5. Lenschow DJ, Ho SG, Sattar H, Rhee L, Gray G, Nabavi N, Herold KC, Bluestone JA (1995) 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 181:1145–1155

    CAS  PubMed  Google Scholar 

  6. Finck BK, Linsley PS, Wofsy D (1994) Treatment of murine lupus with CTLA4Ig. Science 265:1225–1227

    CAS  PubMed  Google Scholar 

  7. Kuchroo VK, Das MP, Brown JA, Ranger AM, Zamvil SS, Sobel RA, Weiner HL, Nabavi N, Glimcher LH (1995) B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 80:707–718

    CAS  PubMed  Google Scholar 

  8. Racke MK, Scott DE, Quigley L, Gray GS, Abe R, June CH, Perrin PJ (1995) Distinct roles for B7-1 (CD-80) and B7-2 (CD-86) in the initiation of experimental allergic encephalomyelitis. J Clin Invest 96:2195–2203

    CAS  PubMed  Google Scholar 

  9. Tang Q, Henriksen KJ, Boden EK, Tooley AJ, Ye J, Subudhi SK, Zheng XX, Strom TB, Bluestone JA (2003) Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 171:3348–3352

    Google Scholar 

  10. Salomon B, Lenschow DJ, Rhee L, Ashourian N, Singh B, Sharpe A, Bluestone JA (2000) B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12:431–440

    Google Scholar 

  11. Lohr J, Knoechel B, Jiang S, Sharpe AH, Abbas AK (2003) The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens. Nat Immunol 4:664–669

    Google Scholar 

  12. Swallow MM, Wallin JJ, Sha WC (1999) B7 h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFalpha. Immunity 11:423–432

    CAS  PubMed  Google Scholar 

  13. Ling V, Wu PW, Finnerty HF, Bean KM, Spaulding V, Fouser LA, Leonard JP, Hunter SE, Zollner R, Thomas JL, Miyashiro JS, Jacobs KA, Collins M (2000) Cutting edge: identification of GL50, a novel B7-like protein that functionally binds to ICOS receptor. J Immunol 164:1653–1657

    Google Scholar 

  14. Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, Kroczek RA (1999) ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397:263–266

    CAS  PubMed  Google Scholar 

  15. 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 (2000) The CD28-related molecule ICOS is required for effective T cell-dependent immune responses. Immunity 13:95–105

    Google Scholar 

  16. McAdam AJ, Chang TT, Lumelsky AE, Greenfield EA, Boussiotis VA, Duke-Cohan JS, Chernova T, Malenkovich N, Jabs C, Kuchroo VK, Ling V, Collins M, Sharpe AH, Freeman GJ (2000) Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells. J Immunol 165:5035–5040

    Google Scholar 

  17. Rottman JB, Smith T, Tonra JR, Ganley K, Bloom T, Silva R, Pierce B, Gutierrez-Ramos JC, Ozkaynak E, Coyle AJ (2001) The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE. Nat Immunol 2:605–611

    Google Scholar 

  18. Dong C, Juedes AE, Temann UA, Shresta S, Allison JP, Ruddle NN, Flavell RA (2001) ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409:97–101

    CAS  PubMed  Google Scholar 

  19. Ozkaynak E, Gao W, Shemmeri N, Wang C, Gutierrez-Ramos JC, Amaral J, Qin S, Rottman JB, Coyle AJ, Hancock WW (2001) Importance of ICOS-B7RP-1 costimulation in acute and chronic allograft rejection. Nat Immunol 2:591–596

    Google Scholar 

  20. Kosuge H, Suzuki J, Gotoh R, Koga N, Ito H, Isobe M, Inobe M, Uede T (2003) Induction of immunologic tolerance to cardiac allograft by simultaneous blockade of inducible co-stimulator and cytotoxic T-lymphocyte antigen 4 pathway. Transplantation 75:1374–1379

    CAS  PubMed  Google Scholar 

  21. Harada H, Salama AD, Sho M, Izawa A, Sandner SE, Ito T, Akiba H, Yagita H, Sharpe AH, Freeman GJ, Sayegh MH (2003) The role of the ICOS-B7 h T cell costimulatory pathway in transplantation immunity. J Clin Invest 112:234–243

    CAS  PubMed  Google Scholar 

  22. Dong H, Zhu G, Tamada K, Chen L (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5:1365–1369

    Google Scholar 

  23. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz JL, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034

    CAS  PubMed  Google Scholar 

  24. Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ (2001) PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2:261–268

    Google Scholar 

  25. Tseng SY, Otsuji M, Gorski K, Huang X, Slansky JE, Pai SI, Shalabi A, Shin T, Pardoll DM, Tsuchiya H (2001) B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med 193:839–846

    CAS  PubMed  Google Scholar 

  26. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800

    Google Scholar 

  27. Tamura H, Dong H, Zhu G, Sica GL, Flies DB, Tamada K, Chen L (2001) B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. Blood 97:1809–1816

    CAS  PubMed  Google Scholar 

  28. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    CAS  PubMed  Google Scholar 

  29. Carter L, Fouser LA, Jussif J, Fitz L, Deng B, Wood CR, Collins M, Honjo T, Freeman GJ, Carreno BM (2002) PD-1:PD-L inhibitory pathway affects both CD4 (+) and CD8 (+) T cells and is overcome by IL-2. Eur J Immunol 32:634–643

    Google Scholar 

  30. Ozkaynak E, Wang L, Goodearl A, McDonald K, Qin S, O’Keefe T, Duong T, Smith T, Gutierrez-Ramos JC, Rottman JB, Coyle AJ, Hancock WW (2002) Programmed death-1 targeting can promote allograft survival. J Immunol 169:6546–6553

    Google Scholar 

  31. Bennett F, Luxenberg D, Ling V, Wang IM, Marquette K, Lowe D, Khan N, Veldman G, Jacobs KA, Valge-Archer VE, Collins M, Carreno BM (2003) Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses. J Immunol 170:711–718

    Google Scholar 

  32. Gao W, Demirci G, Li XC (2003) Negative T cell costimulation and islet tolerance. Diabetes Metab Res Rev 19:179–185

    Google Scholar 

  33. Mazanet MM, Hughes CC (2002) B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis. J Immunol 169:3581–3588

    Google Scholar 

  34. Rodig N, Ryan T, Allen JA, Pang H, Grabie N, Chernova T, Greenfield EA, Liang SC, Sharpe AH, Lichtman AH, Freeman GJ (2003) Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis. Eur J Immunol 33:3117–3126

    Google Scholar 

  35. Selenko-Gebauer N, Majdic O, Szekeres A, Hofler G, Guthann E, Korthauer U, Zlabinger G, Steinberger P, Pickl WF, Stockinger H, Knapp W, Stockl J (2003) B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy. J Immunol 170:3637–3644

    Google Scholar 

  36. Brown JA, Dorfman DM, Ma FR, Sullivan EL, Munoz O, Wood CR, Greenfield EA, Freeman GJ (2003) Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 170:1257–1266

    Google Scholar 

  37. Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9:562–567

    Google Scholar 

  38. Iwai Y, Terawaki S, Ikegawa M, Okazaki T, Honjo T (2003) PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med 198:39–50

    CAS  PubMed  Google Scholar 

  39. Wintterle S, Schreiner B, Mitsdoerffer M, Schneider D, Chen L, Meyermann R, Weller M, Wiendl H (2003) Expression of the b7-related molecule b7–h1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res 63:7462–7467

    CAS  PubMed  Google Scholar 

  40. Gao W, Demirci G, Strom TB, Li XC (2003) Stimulating PD-1-negative signals concurrent with blocking CD154 co-stimulation induces long-term islet allograft survival. Transplantation 76:994–999

    CAS  PubMed  Google Scholar 

  41. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A 99:12293–12297

    CAS  PubMed  Google Scholar 

  42. Ishida Y, Agata Y, Shibahara K, Honjo T (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11:3887–3895

    CAS  PubMed  Google Scholar 

  43. Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T (1996) Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol 8:765–772

    CAS  PubMed  Google Scholar 

  44. Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger LR (1997) Activation-induced expression of human programmed death-1 gene in T-lymphocytes. Exp Cell Res 232:25–28

    Article  CAS  PubMed  Google Scholar 

  45. Nishimura H, Nose M, Hiai H, Minato N, Honjo T (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11:141–151

    CAS  PubMed  Google Scholar 

  46. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama A, Mizoguchi A, Hiai H, Minato N, Honjo T (2001) Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291:319–322

    CAS  PubMed  Google Scholar 

  47. Sharpe AH, Freeman GJ (2002) The B7-CD28 superfamily. Nat Rev Immunol 2:116–126

    Google Scholar 

  48. Liang SC, Latchman YE, Buhlmann JE, Tomczak MF, Horwitz BH, Freeman GJ, Sharpe AH (2003) Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol 33:2706–2716

    Google Scholar 

  49. Ansari MJ, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H, Yamazaki T, Azuma M, Iwai H, Khoury SJ, Auchincloss H Jr, Sayegh MH (2003) The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 198:63–69

    CAS  PubMed  Google Scholar 

  50. Subudhi SK, Zhou P, Yerian LM, Chin RK, Lo JC, Anders RA, Sun Y, Chen L, Wang Y, Alegre ML, Fu YX (2004) Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection. J Clin Invest 113:694–700

    CAS  PubMed  Google Scholar 

  51. Kanai T, Totsuka T, Uraushihara K, Makita S, Nakamura T, Koganei K, Fukushima T, Akiba H, Yagita H, Okumura K, Machida U, Iwai H, Azuma M, Chen L, Watanabe M (2003) Blockade of B7-H1 suppresses the development of chronic intestinal inflammation. J Immunol 171:4156–4163

    Google Scholar 

  52. Blazar BR, Carreno BM, Panoskaltsis-Mortari A, Carter L, Iwai Y, Yagita H, Nishimura H, Taylor PA (2003) Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. J Immunol 171:1272–1277

    Google Scholar 

  53. Liu X, Gao JX, Wen J, Yin L, Li O, Zuo T, Gajewski TF, Fu YX, Zheng P, Liu Y (2003) B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. J Exp Med 197:1721–1730

    CAS  PubMed  Google Scholar 

  54. Salama AD, Chitnis T, Imitola J, Akiba H, Tushima F, Azuma M, Yagita H, Sayegh MH, Khoury SJ (2003) Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis. J Exp Med 198:71–78

    CAS  PubMed  Google Scholar 

  55. Sidorenko SP, Clark EA (2003) The dual-function CD150 receptor subfamily: the viral attraction. Nat Immunol 4:19–24

    Google Scholar 

  56. Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T (2001) PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci U S A 98:13866–13871

    CAS  PubMed  Google Scholar 

  57. Shin T, Kennedy G, Gorski K, Tsuchiya H, Koseki H, Azuma M, Yagita H, Chen L, Powell J, Pardoll D, Housseau F (2003) Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor. J Exp Med 198:31–38

    CAS  PubMed  Google Scholar 

  58. Wang S, Bajorath J, Flies DB, Dong H, Honjo T, Chen L (2003) Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction. J Exp Med 197:1083–1091

    CAS  PubMed  Google Scholar 

  59. Merwe van der PA, Davis SJ (2003) Molecular interactions mediating T cell antigen recognition. Annu Rev Immunol 21:659–684

    Article  PubMed  Google Scholar 

  60. Youngnak P, Kozono Y, Kozono H, Iwai H, Otsuki N, Jin H, Omura K, Yagita H, Pardoll DM, Chen L, Azuma M (2003) Differential binding properties of B7-H1 and B7-DC to programmed death-1. Biochem Biophys Res Commun 307:672–677

    Google Scholar 

  61. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167:1245–1253

    Google Scholar 

  62. Lenschow DJ, Herold KC, Rhee L, Patel B, Koons A, Qin HY, Fuchs E, Singh B, Thompson CB, Bluestone JA (1996) CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes. Immunity 5:285–293

    CAS  PubMed  Google Scholar 

  63. Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, TF Gajewski (2004) PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res 64:1140–1145

    CAS  PubMed  Google Scholar 

  64. Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 4:1206–1212

    Google Scholar 

  65. Nguyen LT, Radhakrishnan S, Ciric B, Tamada K, Shin T, Pardoll DM, Chen L, Rodriguez M, Pease LR (2002) Cross-linking the B7 family molecule B7-DC directly activates immune functions of dendritic cells. J Exp Med 196:1393–1398

    CAS  PubMed  Google Scholar 

  66. Radhakrishnan S, Nguyen LT, Ciric B, Ure DR, Zhou B, Tamada K, Dong H, Tseng SY, Shin T, Pardoll DM, Chen L, Kyle RA, Rodriguez M, Pease LR (2003) Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells. J Immunol 170:1830–1838

    Google Scholar 

  67. Iwai H, Kozono Y, Hirose S, Akiba H, Yagita H, Okumura K, Kohsaka H, Miyasaka N, Azuma M (2002) Amelioration of collagen-induced arthritis by blockade of inducible costimulator-B7 homologous protein costimulation. J Immunol 169:4332–4339

    Google Scholar 

  68. Nurieva RI, Treuting P, Duong J, Flavell RA, Dong C (2003) Inducible costimulator is essential for collagen-induced arthritis. J Clin Invest 111:701–706

    CAS  PubMed  Google Scholar 

  69. Totsuka T, Kanai T, Iiyama R, Uraushihara K, Yamazaki M, Okamoto R, Hibi T, Tezuka K, Azuma M, Akiba H, Yagita H, Okumura K, Watanabe M (2003) Ameliorating effect of anti-inducible costimulator monoclonal antibody in a murine model of chronic colitis. Gastroenterology 124:410–421

    CAS  PubMed  Google Scholar 

  70. Iwai H, Abe M, Hirose S, Tsushima F, Tezuka K, Akiba H, agita H, Okumura K, Kohsaka H, Miyasaka N, Azuma M (2003) Involvement of inducible costimulator-B7 homologous protein costimulatory pathway in murine lupus nephritis. J Immunol 171:2848–2854

    Google Scholar 

  71. Nakamura Y, Yasunami Y, Satoh M, Hirakawa E, Katsuta H, Ono J, Kamada M, Todo S, Nakayama T, Taniguchi M, Ikeda S (2003) Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator. Transplantation 75:1115–1118

    CAS  PubMed  Google Scholar 

  72. Ogawa S, Nagamatsu G, Watanabe M, Watanabe S, Hayashi T, Horita S, Nitta N, Nihei H, Tezuka K, Abe R (2001) Opposing effects of anti-activation-inducible lymphocyte-immunomodulatory molecule/inducible costimulator antibody on the development of acute versus chronic graft-versus-host disease. J Immunol 167:5741–5748

    Google Scholar 

  73. Liu X, Bai XF, Wen J, Gao JX, Liu J, Lu P, Wang Y, Zheng P, Liu Z (2001) B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8 (+) T lymphocytes in vivo. J Exp Med 194:1339–1348

    CAS  PubMed  Google Scholar 

  74. Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, Shin, Tsuchiya H, Pardoll DM, Okumura K, Azuma M, Yagita H (2002) Expression of programmed death 1 ligands by murine T cells and APC. J Immunol 169:5538–5545

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Chicago, 5841 S. Maryland, Chicago, IL, 60637, USA

    Sumit K. Subudhi & Yang-Xin Fu

  2. Department of Medicine, University of Chicago, Chicago, IL, 60637, USA

    Maria-Luisa Alegre

  3. Committee on Immunology, University of Chicago, Chicago, IL, 60637, USA

    Sumit K. Subudhi, Maria-Luisa Alegre & Yang-Xin Fu

Authors
  1. Sumit K. Subudhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria-Luisa Alegre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang-Xin Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yang-Xin Fu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Subudhi, S.K., Alegre, ML. & Fu, YX. The balance of immune responses: costimulation verse coinhibition. J Mol Med 83, 193–202 (2005). https://doi.org/10.1007/s00109-004-0617-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-004-0617-1

Keywords

Search

Navigation