CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation

doi:10.1084/jem.182.2.459

This Article

	Full Text (PDF, 736K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Krummel, M. F.
	Articles by Allison, J. P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Krummel, M. F.
	Articles by Allison, J. P.


Social Bookmarking

	What's this?

ARTICLES

CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation

MF Krummel and JP Allison
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.

The importance of the B7/CD28/CTLA-4 molecules has been established in studies of antigen-presenting cell-derived B7 and its interaction with the T cell costimulatory molecule CD28. CTLA-4, a T cell surface glycoprotein that is related to CD28, can also interact with B7-1 and B7-2. However, less is known about the function of CTLA-4, which is expressed at highest levels after activation. We have generated an antibody to CTLA-4 to investigate the consequences of engagement of this molecule in a carefully defined system using highly purified T cells. We show here that the presence of low levels of B7-2 on freshly explanted T cells can partially inhibit T cell proliferation, and this inhibition is mediated by interactions with CTLA-4. Cross-linking of CTLA-4 together with the TCR and CD28 strongly inhibits proliferation and IL-2 secretion by T cells. Finally, results show that CD28 and CTLA- 4 deliver opposing signals that appear to be integrated by the T cell in determining the response to activation. These data strongly suggest that the outcome of T cell antigen receptor stimulation is regulated by CD28 costimulatory signals, as well as inhibitory signals derived from CTLA-4.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Daroszewski, J., Pawlak, E., Karabon, L., Frydecka, I., Jonkisz, A., Slowik, M., Bolanowski, M. (2009). Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms. Eur J Endocrinol 161: 787-793 [Abstract] [Full Text]
Ansell, S. M., Hurvitz, S. A., Koenig, P. A., LaPlant, B. R., Kabat, B. F., Fernando, D., Habermann, T. M., Inwards, D. J., Verma, M., Yamada, R., Erlichman, C., Lowy, I., Timmerman, J. M. (2009). Phase I Study of Ipilimumab, an Anti-CTLA-4 Monoclonal Antibody, in Patients with Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma. Clin. Cancer Res. 15: 6446-6453 [Abstract] [Full Text]
Coquerelle, C, Oldenhove, G, Acolty, V, Denoeud, J, Vansanten, G, Verdebout, J-M, Mellor, A, Bluestone, J A, Moser, M (2009). Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis. Gut 58: 1363-1373 [Abstract] [Full Text]
Garidou, L., Heydari, S., Truong, P., Brooks, D. G., McGavern, D. B. (2009). Therapeutic Memory T Cells Require Costimulation for Effective Clearance of a Persistent Viral Infection. J. Virol. 83: 8905-8915 [Abstract] [Full Text]
Nakayama, Y., Kim, S.-I., Kim, E. H., Lambris, J. D., Sandor, M., Suresh, M. (2009). C3 Promotes Expansion of CD8+ and CD4+ T Cells in a Listeria monocytogenes Infection. J. Immunol. 183: 2921-2931 [Abstract] [Full Text]
Shieh, S.-J., Chou, F.-C., Yu, P.-N., Lin, W.-C., Chang, D.-M., Roffler, S. R., Sytwu, H.-K. (2009). Transgenic Expression of Single-Chain Anti-CTLA-4 Fv on {beta} Cells Protects Nonobese Diabetic Mice from Autoimmune Diabetes. J. Immunol. 183: 2277-2285 [Abstract] [Full Text]
Robert, C., Ghiringhelli, F. (2009). What Is the Role of Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade in Patients with Metastatic Melanoma?. The Oncologist 14: 848-861 [Abstract] [Full Text]
Kurtz, J., Raval, F., Vallot, C., Der, J., Sykes, M. (2009). CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance. Blood 113: 3475-3484 [Abstract] [Full Text]
Chen, H., Liakou, C. I., Kamat, A., Pettaway, C., Ward, J. F., Tang, D. N., Sun, J., Jungbluth, A. A., Troncoso, P., Logothetis, C., Sharma, P. (2009). Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-{gamma} levels in both nonmalignant and malignant prostate tissues. Proc. Natl. Acad. Sci. USA 106: 2729-2734 [Abstract] [Full Text]
Shvets, A., Chakrabarti, R., Gonzalez-Quintial, R., Baccala, R., Theofilopoulos, A. N., Prud'homme, G. J. (2009). Impaired negative regulation of homeostatically proliferating T cells. Blood 113: 622-625 [Abstract] [Full Text]
Schmidt, E. M., Wang, C. J., Ryan, G. A., Clough, L. E., Qureshi, O. S., Goodall, M., Abbas, A. K., Sharpe, A. H., Sansom, D. M., Walker, L. S. K. (2009). CTLA-4 Controls Regulatory T Cell Peripheral Homeostasis and Is Required for Suppression of Pancreatic Islet Autoimmunity. J. Immunol. 182: 274-282 [Abstract] [Full Text]
Yuan, J., Gnjatic, S., Li, H., Powel, S., Gallardo, H. F., Ritter, E., Ku, G. Y., Jungbluth, A. A., Segal, N. H., Rasalan, T. S., Manukian, G., Xu, Y., Roman, R.-A., Terzulli, S. L., Heywood, M., Pogoriler, E., Ritter, G., Old, L. J., Allison, J. P., Wolchok, J. D. (2008). CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc. Natl. Acad. Sci. USA 105: 20410-20415 [Abstract] [Full Text]
Fong, L., Small, E. J. (2008). Anti-Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment. JCO 26: 5275-5283 [Abstract] [Full Text]
Wolchok, J. D., Saenger, Y. (2008). The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation. The Oncologist 13: 2-9 [Abstract] [Full Text]
Weber, J. (2008). Overcoming Immunologic Tolerance to Melanoma: Targeting CTLA-4 with Ipilimumab (MDX-010). The Oncologist 13: 16-25 [Abstract] [Full Text]
Liakou, C. I., Kamat, A., Tang, D. N., Chen, H., Sun, J., Troncoso, P., Logothetis, C., Sharma, P. (2008). CTLA-4 blockade increases IFN{gamma}-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc. Natl. Acad. Sci. USA 105: 14987-14992 [Abstract] [Full Text]
Quezada, S. A., Peggs, K. S., Simpson, T. R., Shen, Y., Littman, D. R., Allison, J. P. (2008). Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma. JEM 205: 2125-2138 [Abstract] [Full Text]
Matsumura, S., Wang, B., Kawashima, N., Braunstein, S., Badura, M., Cameron, T. O., Babb, J. S., Schneider, R. J., Formenti, S. C., Dustin, M. L., Demaria, S. (2008). Radiation-Induced CXCL16 Release by Breast Cancer Cells Attracts Effector T Cells. J. Immunol. 181: 3099-3107 [Abstract] [Full Text]
Kirkwood, J. M., Tarhini, A. A., Panelli, M. C., Moschos, S. J., Zarour, H. M., Butterfield, L. H., Gogas, H. J. (2008). Next Generation of Immunotherapy for Melanoma. JCO 26: 3445-3455 [Abstract] [Full Text]
Berg, M., Zavazava, N. (2008). Regulation of CD28 expression on CD8+ T cells by CTLA-4. J. Leukoc. Biol. 83: 853-863 [Abstract] [Full Text]
Fasso, M., Waitz, R., Hou, Y., Rim, T., Greenberg, N. M., Shastri, N., Fong, L., Allison, J. P. (2008). SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade. Proc. Natl. Acad. Sci. USA 105: 3509-3514 [Abstract] [Full Text]
Habib-Agahi, M., Phan, T. T., Searle, P. F. (2007). Co-stimulation with 4-1BB ligand allows extended T-cell proliferation, synergizes with CD80/CD86 and can reactivate anergic T cells. Int Immunol 19: 1383-1394 [Abstract] [Full Text]
Borowski, A. B., Boesteanu, A. C., Mueller, Y. M., Carafides, C., Topham, D. J., Altman, J. D., Jennings, S. R., Katsikis, P. D. (2007). Memory CD8+ T Cells Require CD28 Costimulation. J. Immunol. 179: 6494-6503 [Abstract] [Full Text]
Hodi, F. S. (2007). Cytotoxic T-Lymphocyte Associated Antigen-4. Clin. Cancer Res. 13: 5238-5242 [Abstract] [Full Text]
Ribas, A., Hanson, D. C., Noe, D. A., Millham, R., Guyot, D. J., Bernstein, S. H., Canniff, P. C., Sharma, A., Gomez-Navarro, J. (2007). Tremelimumab (CP-675,206), a Cytotoxic T Lymphocyte Associated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer. The Oncologist 12: 873-883 [Abstract] [Full Text]
Bashyam, H. (2007). CTLA-4: From conflict to clinic. JEM 204: 1243-1243 [Abstract] [Full Text]
Chung, J.-S., Sato, K., Dougherty, I. I., Cruz, P. D. Jr, Ariizumi, K. (2007). DC-HIL is a negative regulator of T lymphocyte activation. Blood 109: 4320-4327 [Abstract] [Full Text]
Raue, H.-P., Slifka, M. K. (2007). Pivotal Advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection. J. Leukoc. Biol. 81: 1165-1175 [Abstract] [Full Text]
Kim, G., Levin, M., Schoenberger, S. P., Sharpe, A., Kronenberg, M. (2007). Paradoxical Effect of Reduced Costimulation in T Cell-Mediated Colitis. J. Immunol. 178: 5563-5570 [Abstract] [Full Text]
Pandiyan, P., Hegel, J. K. E., Krueger, M., Quandt, D., Brunner-Weinzierl, M. C. (2007). High IFN-{gamma} Production of Individual CD8 T Lymphocytes Is Controlled by CD152 (CTLA-4). J. Immunol. 178: 2132-2140 [Abstract] [Full Text]
Gattinoni, L., Ranganathan, A., Surman, D. R., Palmer, D. C., Antony, P. A., Theoret, M. R., Heimann, D. M., Rosenberg, S. A., Restifo, N. P. (2006). CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent. Blood 108: 3818-3823 [Abstract] [Full Text]
Lee, C.-h., Kakinuma, T., Wang, J., Zhang, H., Palmer, D. C., Restifo, N. P., Hwang, S. T. (2006). Sensitization of B16 tumor cells with a CXCR4 antagonist increases the efficacy of immunotherapy for established lung metastases.. Molecular Cancer Therapeutics 5: 2592-2599 [Abstract] [Full Text]
Engelhardt, J. J., Sullivan, T. J., Allison, J. P. (2006). CTLA-4 Overexpression Inhibits T Cell Responses through a CD28-B7-Dependent Mechanism. J. Immunol. 177: 1052-1061 [Abstract] [Full Text]
Mukherjee, S., Ahmed, A., Malu, S., Nandi, D. (2006). Modulation of cell cycle progression by CTLA4-CD80/CD86 interactions on CD4+ T cells depends on strength of the CD3 signal: critical role for IL-2. J. Leukoc. Biol. 80: 66-74 [Abstract] [Full Text]
Lee, H. Y., Kim, M.-K., Park, K. S., Shin, E. H., Jo, S. H., Kim, S. D., Jo, E. J., Lee, Y.-N., Lee, C., Baek, S.-H., Bae, Y.-S. (2006). Serum Amyloid A Induces Contrary Immune Responses via Formyl Peptide Receptor-Like 1 in Human Monocytes. Mol. Pharmacol. 70: 241-248 [Abstract] [Full Text]
Fierro, N. A., Pedraza-Alva, G., Rosenstein, Y. (2006). TCR-Dependent Cell Response Is Modulated by the Timing of CD43 Engagement.. J. Immunol. 176: 7346-7353 [Abstract] [Full Text]
Beck, K. E., Blansfield, J. A., Tran, K. Q., Feldman, A. L., Hughes, M. S., Royal, R. E., Kammula, U. S., Topalian, S. L., Sherry, R. M., Kleiner, D., Quezado, M., Lowy, I., Yellin, M., Rosenberg, S. A., Yang, J. C. (2006). Enterocolitis in Patients With Cancer After Antibody Blockade of Cytotoxic T-Lymphocyte-Associated Antigen 4. JCO 24: 2283-2289 [Abstract] [Full Text]
Zheng, S. G., Wang, J. H., Stohl, W., Kim, K. S., Gray, J. D., Horwitz, D. A. (2006). TGF-beta Requires CTLA-4 Early after T Cell Activation to Induce FoxP3 and Generate Adaptive CD4+CD25+ Regulatory Cells. J. Immunol. 176: 3321-3329 [Abstract] [Full Text]
Salvalaggio, P. R. O., Camirand, G., Ariyan, C. E., Deng, S., Rogozinski, L., Basadonna, G. P., Rothstein, D. M. (2006). Antigen Exposure during Enhanced CTLA-4 Expression Promotes Allograft Tolerance In Vivo. J. Immunol. 176: 2292-2298 [Abstract] [Full Text]
Kapadia, D., Fong, L. (2005). CTLA-4 Blockade: Autoimmunity As Treatment. JCO 23: 8926-8928 [Full Text]
Schneider, H., Valk, E., da Rocha Dias, S., Wei, B., Rudd, C. E. (2005). CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function. Proc. Natl. Acad. Sci. USA 102: 12861-12866 [Abstract] [Full Text]
Kim, J., Myers, A. C., Chen, L., Pardoll, D. M., Truong-Tran, Q.-A., Lane, A. P., McDyer, J. F., Fortuno, L., Schleimer, R. P. (2005). Constitutive and Inducible Expression of B7 Family of Ligands by Human Airway Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 33: 280-289 [Abstract] [Full Text]
Mukherjee, S., Ahmed, A., Nandi, D. (2005). CTLA4-CD80/CD86 interactions on primary mouse CD4+ T cells integrate signal-strength information to modulate activation with Concanavalin A. J. Leukoc. Biol. 78: 144-157 [Abstract] [Full Text]
Triozzi, P. L., Allen, K. O., Carlisle, R. R., Craig, M., LoBuglio, A. F., Conry, R. M. (2005). Phase I Study of the Intratumoral Administration of Recombinant Canarypox Viruses Expressing B7.1 and Interleukin 12 in Patients with Metastatic Melanoma. Clin. Cancer Res. 11: 4168-4175 [Abstract] [Full Text]
Dillon, T. J., Carey, K. D., Wetzel, S. A., Parker, D. C., Stork, P. J. S. (2005). Regulation of the Small GTPase Rap1 and Extracellular Signal-Regulated Kinases by the Costimulatory Molecule CTLA-4. Mol. Cell. Biol. 25: 4117-4128 [Abstract] [Full Text]
Hodge, J. W., Chakraborty, M., Kudo-Saito, C., Garnett, C. T., Schlom, J. (2005). Multiple Costimulatory Modalities Enhance CTL Avidity. J. Immunol. 174: 5994-6004 [Abstract] [Full Text]
Loser, K., Scherer, A., Krummen, M. B. W., Varga, G., Higuchi, T., Schwarz, T., Sharpe, A. H., Grabbe, S., Bluestone, J. A., Beissert, S. (2005). An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice. J. Immunol. 174: 5298-5305 [Abstract] [Full Text]
Mead, K. I., Zheng, Y., Manzotti, C. N., Perry, L. C. A., Liu, M. K. P., Burke, F., Powner, D. J., Wakelam, M. J. O., Sansom, D. M. (2005). Exocytosis of CTLA-4 Is Dependent on Phospholipase D and ADP Ribosylation Factor-1 and Stimulated during Activation of Regulatory T Cells. J. Immunol. 174: 4803-4811 [Abstract] [Full Text]
Glennie, S., Soeiro, I., Dyson, P. J., Lam, E. W.-F., Dazzi, F. (2005). Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105: 2821-2827 [Abstract] [Full Text]
Saudemont, A., Jouy, N., Hetuin, D., Quesnel, B. (2005). NK cells that are activated by CXCL10 can kill dormant tumor cells that resist CTL-mediated lysis and can express B7-H1 that stimulates T cells. Blood 105: 2428-2435 [Abstract] [Full Text]
Davidson, A, Diamond, B, Wofsy, D, Daikh, D (2005). Block and tackle: CTLA4Ig takes on lupus. Lupus 14: 197-203 [Abstract]
Zheng, Y., Jost, M., Gaughan, J. P., Class, R., Coyle, A. J., Monestier, M. (2005). ICOS-B7 Homologous Protein Interactions Are Necessary for Mercury-Induced Autoimmunity. J. Immunol. 174: 3117-3121 [Abstract] [Full Text]
May, K. F. Jr, Roychowdhury, S., Bhatt, D., Kocak, E., Bai, X.-F., Liu, J.-Q., Ferketich, A. K., Martin, E. W. Jr, Caligiuri, M. A., Zheng, P., Liu, Y. (2005). Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies. Blood 105: 1114-1120 [Abstract] [Full Text]
Demaria, S., Kawashima, N., Yang, A. M., Devitt, M. L., Babb, J. S., Allison, J. P., Formenti, S. C. (2005). Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast Cancer. Clin. Cancer Res. 11: 728-734 [Abstract] [Full Text]
van Wijk, F., Hoeks, S., Nierkens, S., Koppelman, S. J., van Kooten, P., Boon, L., Knippels, L. M. J., Pieters, R. (2005). CTLA-4 Signaling Regulates the Intensity of Hypersensitivity Responses to Food Antigens, but is Not Decisive in the Induction of Sensitization. J. Immunol. 174: 174-179 [Abstract] [Full Text]
Roden, A. C., Moser, M. T., Tri, S. D., Mercader, M., Kuntz, S. M., Dong, H., Hurwitz, A. A., McKean, D. J., Celis, E., Leibovich, B. C., Allison, J. P., Kwon, E. D. (2004). Augmentation of T Cell Levels and Responses Induced by Androgen Deprivation. J. Immunol. 173: 6098-6108 [Abstract] [Full Text]
Saudemont, A., Quesnel, B. (2004). In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis. Blood 104: 2124-2133 [Abstract] [Full Text]
Singh, A., Svaren, J., Grayson, J., Suresh, M. (2004). CD8 T Cell Responses to Lymphocytic Choriomeningitis Virus in Early Growth Response Gene 1-Deficient Mice. J. Immunol. 173: 3855-3862 [Abstract] [Full Text]
Vasu, C., Prabhakar, B. S., Holterman, M. J. (2004). Targeted CTLA-4 Engagement Induces CD4+CD25+CTLA-4high T Regulatory Cells with Target (Allo)antigen Specificity. J. Immunol. 173: 2866-2876 [Abstract] [Full Text]
Daftarian, P., Song, G.-Y., Ali, S., Faynsod, M., Longmate, J., Diamond, D. J., Ellenhorn, J. D. I. (2004). Two Distinct Pathways of Immuno-Modulation Improve Potency of p53 Immunization in Rejecting Established Tumors. Cancer Res. 64: 5407-5414 [Abstract] [Full Text]
Stohl, W., Xu, D., Kim, K. S., David, C. S., Allison, J. P. (2004). MHC class II-independent and -dependent T cell expansion and B cell hyperactivity in vivo in mice deficient in CD152 (CTLA-4). Int Immunol 16: 895-904 [Abstract] [Full Text]
den Brok, M. H. M. G. M., Sutmuller, R. P. M., van der Voort, R., Bennink, E. J., Figdor, C. G., Ruers, T. J. M., Adema, G. J. (2004). In Situ Tumor Ablation Creates an Antigen Source for the Generation of Antitumor Immunity. Cancer Res. 64: 4024-4029 [Abstract] [Full Text]
Balkhi, M. Y., Latchumanan, V. K., Singh, B., Sharma, P., Natarajan, K. (2004). Cross-regulation of CD86 by CD80 differentially regulates T helper responses from Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets. J. Leukoc. Biol. 75: 874-883 [Abstract] [Full Text]
Jovasevic, V. M., Gorelik, L., Bluestone, J. A., Mokyr, M. B. (2004). Importance of IL-10 for CTLA-4-Mediated Inhibition of Tumor-Eradicating Immunity. J. Immunol. 172: 1449-1454 [Abstract] [Full Text]
Prabhakar, B. S., Bahn, R. S., Smith, T. J. (2003). Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy. Endocr. Rev. 24: 802-835 [Abstract] [Full Text]
Keler, T., Halk, E., Vitale, L., O'Neill, T., Blanset, D., Lee, S., Srinivasan, M., Graziano, R. F., Davis, T., Lonberg, N., Korman, A. (2003). Activity and Safety of CTLA-4 Blockade Combined with Vaccines in Cynomolgus Macaques. J. Immunol. 171: 6251-6259 [Abstract] [Full Text]
Murillo, O., Arina, A., Tirapu, I., Alfaro, C., Mazzolini, G., Palencia, B., De Cerio, A. L.-D., Prieto, J., Bendandi, M., Melero, I. (2003). Potentiation of Therapeutic Immune Responses against Malignancies with Monoclonal Antibodies. Clin. Cancer Res. 9: 5454-5464 [Abstract] [Full Text]
Santulli-Marotto, S., Nair, S. K., Rusconi, C., Sullenger, B., Gilboa, E. (2003). Multivalent RNA Aptamers That Inhibit CTLA-4 and Enhance Tumor Immunity. Cancer Res. 63: 7483-7489 [Abstract] [Full Text]
Agadjanyan, M. G., Chattergoon, M. A., Holterman, M. J., Monzavi-Karbassi, B., Kim, J. J., Dentchev, T., Wilson, D., Ayyavoo, V., Montaner, L. J., Kieber-Emmons, T., Sekaly, R.-P., Weiner, D. B. (2003). Costimulatory Molecule Immune Enhancement in a Plasmid Vaccine Model Is Regulated in Part Through the Ig Constant-Like Domain of CD80/86. J. Immunol. 171: 4311-4319 [Abstract] [Full Text]
Maszyna, F., Hoff, H., Kunkel, D., Radbruch, A., Brunner-Weinzierl, M. C. (2003). Diversity of Clonal T Cell Proliferation Is Mediated by Differential Expression of CD152 (CTLA-4) on the Cell Surface of Activated Individual T Lymphocytes. J. Immunol. 171: 3459-3466 [Abstract] [Full Text]
Zheng, Y., Monestier, M. (2003). Inhibitory Signal Override Increases Susceptibility to Mercury-Induced Autoimmunity. J. Immunol. 171: 1596-1601 [Abstract] [Full Text]
Yagi, J., Arimura, Y., Dianzani, U., Uede, T., Okamoto, T., Uchiyama, T. (2003). Regulatory Roles of IL-2 and IL-4 in H4/Inducible Costimulator Expression on Activated CD4+ T Cells During Th Cell Development. J. Immunol. 171: 783-794 [Abstract] [Full Text]
Hwang, I., Shen, X., Sprent, J. (2003). Direct stimulation of naive T cells by membrane vesicles from antigen-presenting cells: Distinct roles for CD54 and B7 molecules. Proc. Natl. Acad. Sci. USA 100: 6670-6675 [Abstract] [Full Text]
Kurosawa, S., Myers, A. C., Chen, L., Wang, S., Ni, J., Plitt, J. R., Heller, N. M., Bochner, B. S., Schleimer, R. P. (2003). Expression of the Costimulatory Molecule B7-H2 (Inducible Costimulator Ligand) by Human Airway Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 28: 563-573 [Abstract] [Full Text]
Espenschied, J., Lamont, J., Longmate, J., Pendas, S., Wang, Z., Diamond, D. J., Ellenhorn, J. D. I. (2003). CTLA-4 Blockade Enhances the Therapeutic Effect of an Attenuated Poxvirus Vaccine Targeting p53 in an Established Murine Tumor Model. J. Immunol. 170: 3401-3407 [Abstract] [Full Text]
Mochizuki, M., Amemiya, S., Kobayashi, K., Kobayashi, K., Shimura, Y., Ishihara, T., Nakagomi, Y., Onigata, K., Tamai, S., Kasuga, A., Nanazawa, S. (2003). Association of the CTLA-4 Gene 49 A/G Polymorphism With Type 1 Diabetes and Autoimmune Thyroid Disease in Japanese Children. Diabetes Care 26: 843-847 [Abstract] [Full Text]
Steel, C., Nutman, T. B. (2003). CTLA-4 in Filarial Infections: Implications for a Role in Diminished T Cell Reactivity. J. Immunol. 170: 1930-1938 [Abstract] [Full Text]
Vacchio, M. S., Hodes, R. J. (2003). CD28 Costimulation Is Required for In Vivo Induction of Peripheral Tolerance in CD8 T Cells. JEM 197: 19-26 [Abstract] [Full Text]
Yin, L., Schneider, H., Rudd, C. E. (2003). Short cytoplasmic SDYMNM segment of CD28 is sufficient to convert CTLA-4 to a positive signaling receptor. J. Leukoc. Biol. 73: 178-182 [Abstract] [Full Text]
Pistillo, M. P., Tazzari, P. L., Palmisano, G. L., Pierri, I., Bolognesi, A., Ferlito, F., Capanni, P., Polito, L., Ratta, M., Pileri, S., Piccioli, M., Basso, G., Rissotto, L., Conte, R., Gobbi, M., Stirpe, F., Ferrara, G. B. (2003). CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells. Blood 101: 202-209 [Abstract] [Full Text]
Kang, J. L., Lee, H. S., Jung, H. J., Kim, H. J., Hah, J. S., Castranova, V. (2002). Inhibition of Mitogenic Stimulant-Induced Activation of Thymocytes with Zinc Tetrakis-(N-Methyl-4'-Pyridyl) Porphyrinato. J. Pharmacol. Exp. Ther. 303: 1138-1144 [Abstract] [Full Text]
Walker, L. S. K., Ausubel, L. J., Chodos, A., Bekarian, N., Abbas, A. K. (2002). CTLA-4 Differentially Regulates T Cell Responses to Endogenous Tissue Protein Versus Exogenous Immunogen. J. Immunol. 169: 6202-6209 [Abstract] [Full Text]
Vendetti, S., Riccomi, A., Sacchi, A., Gatta, L., Pioli, C., De Magistris, M. T. (2002). Cyclic Adenosine 5'-Monophosphate and Calcium Induce CD152 (CTLA-4) Up-Regulation in Resting CD4+ T Lymphocytes. J. Immunol. 169: 6231-6235 [Abstract] [Full Text]
Montagnoli, C., Bacci, A., Bozza, S., Gaziano, R., Mosci, P., Sharpe, A. H., Romani, L. (2002). B7/CD28-Dependent CD4+CD25+ Regulatory T Cells Are Essential Components of the Memory-Protective Immunity to Candida albicans. J. Immunol. 169: 6298-6308 [Abstract] [Full Text]
Mukherjee, S., Maiti, P. K., Nandi, D. (2002). Role of CD80, CD86, and CTLA4 on mouse CD4+ T lymphocytes in enhancing cell-cycle progression and survival after activation with PMA and ionomycin. J. Leukoc. Biol. 72: 921-931 [Abstract] [Full Text]
Schneider, H., Mandelbrot, D. A., Greenwald, R. J., Ng, F., Lechler, R., Sharpe, A. H., Rudd, C. E. (2002). Cutting Edge: CTLA-4 (CD152) Differentially Regulates Mitogen-Activated Protein Kinases (Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase) in CD4+ T Cells from Receptor/Ligand-Deficient Mice. J. Immunol. 169: 3475-3479 [Abstract] [Full Text]
Tivol, E. A., Gorski, J. (2002). Re-establishing Peripheral Tolerance in the Absence of CTLA-4: Complementation by Wild-Type T Cells Points to an Indirect Role for CTLA-4. J. Immunol. 169: 1852-1858 [Abstract] [Full Text]
Fallarino, F., Grohmann, U., Vacca, C., Bianchi, R., Fioretti, M. C., Puccetti, P. (2002). CD40 Ligand and CTLA-4 Are Reciprocally Regulated in the Th1 Cell Proliferative Response Sustained by CD8+ Dendritic Cells. J. Immunol. 169: 1182-1188 [Abstract] [Full Text]
Hwang, K. W., Sweatt, W. B., Brown, I. E., Blank, C., Gajewski, T. F., Bluestone, J. A., Alegre, M.-L. (2002). Cutting Edge: Targeted Ligation of CTLA-4 In Vivo by Membrane-Bound Anti-CTLA-4 Antibody Prevents Rejection of Allogeneic Cells. J. Immunol. 169: 633-637 [Abstract] [Full Text]
Arimura, Y., Kato, H., Dianzani, U., Okamoto, T., Kamekura, S., Buonfiglio, D., Miyoshi-Akiyama, T., Uchiyama, T., Yagi, J. (2002). A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells and regulates their responses. Int Immunol 14: 555-566 [Abstract] [Full Text]
Graca, L., Thompson, S., Lin, C.-Y., Adams, E., Cobbold, S. P., Waldmann, H. (2002). Both CD4+CD25+ and CD4+CD25- Regulatory Cells Mediate Dominant Transplantation Tolerance. J. Immunol. 168: 5558-5565 [Abstract] [Full Text]
Guntermann, C., Alexander, D. R. (2002). CTLA-4 Suppresses Proximal TCR Signaling in Resting Human CD4+ T Cells by Inhibiting ZAP-70 Tyr319 Phosphorylation: A Potential Role for Tyrosine Phosphatases. J. Immunol. 168: 4420-4429 [Abstract] [Full Text]
Bai, X.-F., Liu, J., May, K. F. Jr, Guo, Y., Zheng, P., Liu, Y. (2002). B7-CTLA4 interaction promotes cognate destruction of tumor cells by cytotoxic T lymphocytes in vivo. Blood 99: 2880-2889 [Abstract] [Full Text]
Comer, R. M., King, W. J., Ardjomand, N., Theoharis, S., George, A. J. T., Larkin, D. F. P. (2002). Effect of Administration of CTLA4-Ig as Protein or cDNA on Corneal Allograft Survival. IOVS 43: 1095-1103 [Abstract] [Full Text]
Ohnuma, K., Munakata, Y., Ishii, T., Iwata, S., Kobayashi, S., Hosono, O., Kawasaki, H., Dang, N. H., Morimoto, C. (2001). Soluble CD26/Dipeptidyl Peptidase IV Induces T Cell Proliferation Through CD86 Up-Regulation on APCs. J. Immunol. 167: 6745-6755 [Abstract] [Full Text]
Martin, M., Schneider, H., Azouz, A., Rudd, C. E. (2001). Cytotoxic T Lymphocyte Antigen 4 and CD28 Modulate Cell Surface Raft Expression in Their Regulation of T Cell Function. JEM 194: 1675-1682 [Abstract] [Full Text]
Vanasek, T. L., Khoruts, A., Zell, T., Mueller, D. L. (2001). Antagonistic Roles for CTLA-4 and the Mammalian Target of Rapamycin in the Regulation of Clonal Anergy: Enhanced Cell Cycle Progression Promotes Recall Antigen Responsiveness. J. Immunol. 167: 5636-5644 [Abstract] [Full Text]