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*
Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115;
Department of Pathology, Harvard Medical School, Boston, MA 02115;
Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115;
§
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115;
¶
Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; and
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Department of Immunology, Genetics Institute, Cambridge, MA 02140
The inducible costimulatory (ICOS) molecule is expressed by
activated T cells and has homology to CD28 and CD152. ICOS binds B7h, a
molecule expressed by APC with homology to CD80 and CD86. To
investigate regulation of ICOS expression and its role in Th responses
we developed anti-mouse ICOS mAbs and ICOS-Ig fusion protein.
Little ICOS is expressed by freshly isolated mouse T cells, but ICOS is
rapidly up-regulated on most CD4+ and CD8+ T
cells following stimulation of the TCR. Strikingly, ICOS up-regulation
is significantly reduced in the absence of CD80 and CD86 and can be
restored by CD28 stimulation, suggesting that CD28-CD80/CD86
interactions may optimize ICOS expression. Interestingly,
TCR-transgenic T cells differentiated into Th2 expressed significantly
more ICOS than cells differentiated into Th1. We used two methods to
investigate the role of ICOS in activation of CD4+ T cells.
First, CD4+ cells were stimulated with beads coated with
anti-CD3 and either B7h-Ig fusion protein or control Ig fusion
protein. ICOS stimulation enhanced proliferation of CD4+
cells and production of IFN-
, IL-4, and IL-10, but not IL-2.
Second, TCR-transgenic CD4+ T cells were stimulated with
peptide and APC in the presence of ICOS-Ig or control Ig. When the
ICOS:B7h interaction was blocked by ICOS-Ig, CD4+ T cells
produced more IFN- and less IL-4 and IL-10 than CD4+
cells differentiated with control Ig. These results demonstrate that
ICOS stimulation is important in T cell activation and that ICOS may
have a particularly important role in development of Th2
cells.
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V. Dardalhon, A. S. Schubart, J. Reddy, J. H. Meyers, L. Monney, C. A. Sabatos, R. Ahuja, K. Nguyen, G. J. Freeman, E. A. Greenfield, et al. CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector Functions J. Immunol., August 1, 2005; 175(3): 1558 - 1565. [Abstract] [Full Text] [PDF]
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M. E. A. T. van Berkel, E. H. R. Schrijver, F. M. A. Hofhuis, A. H. Sharpe, A. J. Coyle, C. P. Broeren, K. Tesselaar, and M. A. Oosterwegel ICOS Contributes to T Cell Expansion in CTLA-4 Deficient Mice J. Immunol., July 1, 2005; 175(1): 182 - 188. [Abstract] [Full Text] [PDF]
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B. U. Gajewska, A. Tafuri, F. K. Swirski, T. Walker, J. R. Johnson, T. Shea, A. Shahinian, S. Goncharova, T. W. Mak, M. R. Stampfli, et al. B7RP-1 Is Not Required for the Generation of Th2 Responses in a Model of Allergic Airway Inflammation but Is Essential for the Induction of Inhalation Tolerance J. Immunol., March 1, 2005; 174(5): 3000 - 3005. [Abstract] [Full Text] [PDF]
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Y. Zheng, M. Jost, J. P. Gaughan, R. Class, A. J. Coyle, and M. Monestier ICOS-B7 Homologous Protein Interactions Are Necessary for Mercury-Induced Autoimmunity J. Immunol., March 1, 2005; 174(5): 3117 - 3121. [Abstract] [Full Text] [PDF]
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M. Watanabe, S. Watanabe, Y. Hara, Y. Harada, M. Kubo, K. Tanabe, H. Toma, and R. Abe ICOS-Mediated Costimulation on Th2 Differentiation Is Achieved by the Enhancement of IL-4 Receptor-Mediated Signaling J. Immunol., February 15, 2005; 174(4): 1989 - 1996. [Abstract] [Full Text] [PDF]
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C. M. Krawczyk, R. G. Jones, A. Atfield, K. Bachmaier, S. Arya, B. Odermatt, P. S. Ohashi, and J. M. Penninger Differential Control of CD28-Regulated In Vivo Immunity by the E3 Ligase Cbl-b J. Immunol., February 1, 2005; 174(3): 1472 - 1478. [Abstract] [Full Text] [PDF]
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M. Kohyama, D. Sugahara, S. Sugiyama, H. Yagita, K. Okumura, and N. Hozumi Inducible costimulator-dependent IL-10 production by regulatory T cells specific for self-antigen PNAS, March 23, 2004; 101(12): 4192 - 4197. [Abstract] [Full Text] [PDF]
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Y. Arimura, F. Shiroki, S. Kuwahara, H. Kato, U. Dianzani, T. Uchiyama, and J. Yagi Akt Is a Neutral Amplifier for Th Cell Differentiation J. Biol. Chem., March 19, 2004; 279(12): 11408 - 11416. [Abstract] [Full Text] [PDF]
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Y. P. de Jong, S. T. Rietdijk, W. A. Faubion, A. C. Abadia-Molina, K. Clarke, E. Mizoguchi, J. Tian, T. Delaney, S. Manning, J.-C. Gutierrez-Ramos, et al. Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis Int. Immunol., February 1, 2004; 16(2): 205 - 213. [Abstract] [Full Text] [PDF]
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K. Attanavanich and J. F. Kearney Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells J. Immunol., January 15, 2004; 172(2): 803 - 811. [Abstract] [Full Text] [PDF]
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A. B. Stavitsky Regulation of Granulomatous Inflammation in Experimental Models of Schistosomiasis Infect. Immun., January 1, 2004; 72(1): 1 - 12. [Full Text] [PDF]
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H. M. Finney, A. N. Akbar, and A. D. G. Lawson Activation of Resting Human Primary T Cells with Chimeric Receptors: Costimulation from CD28, Inducible Costimulator, CD134, and CD137 in Series with Signals from the TCR{zeta} Chain J. Immunol., January 1, 2004; 172(1): 104 - 113. [Abstract] [Full Text] [PDF]
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H. Iwai, M. Abe, S. Hirose, F. Tsushima, K. Tezuka, H. Akiba, H. Yagita, K. Okumura, H. Kohsaka, N. Miyasaka, et al. Involvement of Inducible Costimulator-B7 Homologous Protein Costimulatory Pathway in Murine Lupus Nephritis J. Immunol., September 15, 2003; 171(6): 2848 - 2854. [Abstract] [Full Text] [PDF]
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S.-C. Wong, E. Oh, C.-H. Ng, and K.-P. Lam Impaired germinal center formation and recall T-cell-dependent immune responses in mice lacking the costimulatory ligand B7-H2 Blood, August 15, 2003; 102(4): 1381 - 1388. [Abstract] [Full Text] [PDF]
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J. Yagi, Y. Arimura, U. Dianzani, T. Uede, T. Okamoto, and T. Uchiyama Regulatory Roles of IL-2 and IL-4 in H4/Inducible Costimulator Expression on Activated CD4+ T Cells During Th Cell Development J. Immunol., July 15, 2003; 171(2): 783 - 794. [Abstract] [Full Text] [PDF]
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L. I. Rutitzky, E. Ozkaynak, J. B. Rottman, and M. J. Stadecker Disruption of the ICOS-B7RP-1 Costimulatory Pathway Leads to Enhanced Hepatic Immunopathology and Increased Gamma Interferon Production by CD4 T Cells in Murine Schistosomiasis Infect. Immun., July 1, 2003; 71(7): 4040 - 4044. [Abstract] [Full Text] [PDF]
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R. V. Parry, C. A. Rumbley, L. H. Vandenberghe, C. H. June, and J. L. Riley 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., July 1, 2003; 171(1): 166 - 174. [Abstract] [Full Text] [PDF]
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 H. Futamatsu, J.-i. Suzuki, H. Kosuge, O. Yokoseki, M. Kamada, H. Ito, M. Inobe, M. Isobe, and T. Uede Attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway Cardiovasc Res, July 1, 2003; 59(1): 95 - 104. [Abstract] [Full Text] [PDF]
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R. E. Wiley, S. Goncharova, T. Shea, J. R. Johnson, A. J. Coyle, and M. Jordana Evaluation of Inducible Costimulator/B7-Related Protein-1 as a Therapeutic Target in a Murine Model of Allergic Airway Inflammation Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 722 - 730. [Abstract] [Full Text] [PDF]
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J. E. Buhlmann, S. K. Elkin, and A. H. Sharpe A Role for the B7-1/B7-2:CD28/CTLA-4 Pathway During Negative Selection J. Immunol., June 1, 2003; 170(11): 5421 - 5428. [Abstract] [Full Text] [PDF]
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S. Kurosawa, A. C. Myers, L. Chen, S. Wang, J. Ni, J. R. Plitt, N. M. Heller, B. S. Bochner, and R. P. Schleimer Expression of the Costimulatory Molecule B7-H2 (Inducible Costimulator Ligand) by Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., May 1, 2003; 28(5): 563 - 573. [Abstract] [Full Text] [PDF]
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K. M. Smith, J. M. Brewer, P. Webb, A. J. Coyle, C. Gutierrez-Ramos, and P. Garside Inducible Costimulatory Molecule-B7-Related Protein 1 Interactions Are Important for the Clonal Expansion and B Cell Helper Functions of Naive, Th1, and Th2 T Cells J. Immunol., March 1, 2003; 170(5): 2310 - 2315. [Abstract] [Full Text] [PDF]
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M. Lohning, A. Hutloff, T. Kallinich, H. W. Mages, K. Bonhagen, A. Radbruch, E. Hamelmann, and R. A. Kroczek Expression of ICOS In Vivo Defines CD4+ Effector T Cells with High Inflammatory Potential and a Strong Bias for Secretion of Interleukin 10 J. Exp. Med., January 20, 2003; 197(2): 181 - 193. [Abstract] [Full Text] [PDF]
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Y. Harada, D. Ohgai, R. Watanabe, K. Okano, O. Koiwai, K. Tanabe, H. Toma, A. Altman, and R. Abe A Single Amino Acid Alteration in Cytoplasmic Domain Determines IL-2 Promoter Activation by Ligation of CD28 but Not Inducible Costimulator (ICOS) J. Exp. Med., January 20, 2003; 197(2): 257 - 262. [Abstract] [Full Text] [PDF]
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L. S. K. Walker, H. E. Wiggett, F. M. C. Gaspal, C. R. Raykundalia, M. D. Goodall, K.-M. Toellner, and P. J. L. Lane Established T Cell-Driven Germinal Center B Cell Proliferation Is Independent of CD28 Signaling but Is Tightly Regulated Through CTLA-4 J. Immunol., January 1, 2003; 170(1): 91 - 98. [Abstract] [Full Text] [PDF]
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H.-W. Mittrucker, M. Kursar, A. Kohler, D. Yanagihara, S. K. Yoshinaga, and S. H. E. Kaufmann Inducible Costimulator Protein Controls the Protective T Cell Response Against Listeria monocytogenes J. Immunol., November 15, 2002; 169(10): 5813 - 5817. [Abstract] [Full Text] [PDF]
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H. Iwai, Y. Kozono, S. Hirose, H. Akiba, H. Yagita, K. Okumura, H. Kohsaka, N. Miyasaka, and M. Azuma Amelioration of Collagen-Induced Arthritis by Blockade of Inducible Costimulator-B7 Homologous Protein Costimulation J. Immunol., October 15, 2002; 169(8): 4332 - 4339. [Abstract] [Full Text] [PDF]
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K. Ogasawara, S. K. Yoshinaga, and L. L. Lanier Inducible Costimulator Costimulates Cytotoxic Activity and IFN-{gamma} Production in Activated Murine NK Cells J. Immunol., October 1, 2002; 169(7): 3676 - 3685. [Abstract] [Full Text] [PDF]
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E. N. Villegas, L. A. Lieberman, N. Mason, S. L. Blass, V. P. Zediak, R. Peach, T. Horan, S. Yoshinaga, and C. A. Hunter A Role for Inducible Costimulator Protein in the CD28- Independent Mechanism of Resistance to Toxoplasma gondii J. Immunol., July 15, 2002; 169(2): 937 - 943. [Abstract] [Full Text] [PDF]
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L. Liang, E. M. Porter, and W. C. Sha Constitutive Expression of the B7h Ligand for Inducible Costimulator on Naive B Cells Is Extinguished after Activation by Distinct B Cell Receptor and Interleukin 4 Receptor-mediated Pathways and Can Be Rescued by CD40 Signaling J. Exp. Med., July 1, 2002; 196(1): 97 - 108. [Abstract] [Full Text] [PDF]
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Y. Arimura, H. Kato, U. Dianzani, T. Okamoto, S. Kamekura, D. Buonfiglio, T. Miyoshi-Akiyama, T. Uchiyama, and J. Yagi A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells and regulates their responses Int. Immunol., June 1, 2002; 14(6): 555 - 566. [Abstract] [Full Text] [PDF]
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P. Wahl, R. Schoop, G. Bilic, J. Neuweiler, M. Le Hir, S. K. Yoshinaga, and R. P. Wuthrich Renal Tubular Epithelial Expression of the Costimulatory Molecule B7RP-1 (Inducible Costimulator Ligand) J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1517 - 1526. [Abstract] [Full Text] [PDF]
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J. Deng, R. H. Dekruyff, G. J. Freeman, D. T. Umetsu, and S. Levy Critical role of CD81 in cognate T-B cell interactions leading to Th2 responses Int. Immunol., May 1, 2002; 14(5): 513 - 523. [Abstract] [Full Text] [PDF]
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A. Yamada, A. D. Salama, and M. H. Sayegh The Role of Novel T Cell Costimulatory Pathways in Autoimmunity and Transplantation J. Am. Soc. Nephrol., February 1, 2002; 13(2): 559 - 575. [Full Text] [PDF]
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R. J. Greenwald, A. J. McAdam, D. Van der Woude, A. R. Satoskar, and A. H. Sharpe Cutting Edge: Inducible Costimulator Protein Regulates Both Th1 and Th2 Responses to Cutaneous Leishmaniasis J. Immunol., February 1, 2002; 168(3): 991 - 995. [Abstract] [Full Text] [PDF]
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G. Richter, M. Hayden-Ledbetter, M. Irgang, J. A. Ledbetter, J. Westermann, I. Korner, K. Daemen, E. A. Clark, A. Aicher, and A. Pezzutto Tumor Necrosis Factor-alpha Regulates the Expression of Inducible Costimulator Receptor Ligand on CD34+ Progenitor Cells during Differentiation into Antigen Presenting Cells J. Biol. Chem., November 30, 2001; 276(49): 45686 - 45693. [Abstract] [Full Text] [PDF]
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S.-h. Ogawa, G. Nagamatsu, M. Watanabe, S. Watanabe, T. Hayashi, S. Horita, K. Nitta, H. Nihei, K. Tezuka, and R. Abe 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., November 15, 2001; 167(10): 5741 - 5748. [Abstract] [Full Text] [PDF]
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J. Hernandez, S. Aung, W. L. Redmond, and L. A. Sherman Phenotypic and Functional Analysis of Cd8+ T Cells Undergoing Peripheral Deletion in Response to Cross-Presentation of Self-Antigen J. Exp. Med., September 17, 2001; 194(6): 707 - 718. [Abstract] [Full Text] [PDF]
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A. G. Tesciuba, S. Subudhi, R. P. Rother, S. J. Faas, A. M. Frantz, D. Elliot, J. Weinstock, L. A. Matis, J. A. Bluestone, and A. I. Sperling Inducible Costimulator Regulates Th2-Mediated Inflammation, but Not Th2 Differentiation, in a Model of Allergic Airway Disease J. Immunol., August 15, 2001; 167(4): 1996 - 2003. [Abstract] [Full Text] [PDF]
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J. J. Wallin, L. Liang, A. Bakardjiev, and W. C. Sha Enhancement of CD8+ T Cell Responses by ICOS/B7h Costimulation J. Immunol., July 1, 2001; 167(1): 132 - 139. [Abstract] [Full Text] [PDF]
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J. Guo, M. Stolina, J. V. Bready, S. Yin, T. Horan, S. K. Yoshinaga, and G. Senaldi Stimulatory Effects of B7-Related Protein-1 on Cellular and Humoral Immune Responses in Mice J. Immunol., May 1, 2001; 166(9): 5578 - 5584. [Abstract] [Full Text] [PDF]
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S. Wang, G. Zhu, K. Tamada, L. Chen, and J. Bajorath Ligand Binding Sites of Inducible Costimulator and High Avidity Mutants with Improved Function J. Exp. Med., April 15, 2002; 195(8): 1033 - 1041. [Abstract] [Full Text] [PDF]
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