Original Article

Cell Contact–dependent Immunosuppression by CD4⁺CD25⁺ Regulatory T Cells Is Mediated by Cell Surface–bound Transforming Growth Factor ß

Correspondence to: Warren Strober, National Institutes of Health, Building 10, Rm. 11N238, 10 Center Dr., Bethesda, MD 20892. Tel:301-496-6810 Fax:301-402-2240 E-mail:wstrober{at}niaid.nih.gov.

CD4⁺CD25⁺ T cells have been identified as a population of immunoregulatory T cells, which mediate suppression of CD4⁺CD25^- T cells by cell–cell contact and not secretion of suppressor cytokines. In this study, we demonstrated that CD4⁺CD25⁺ T cells do produce high levels of transforming growth factor (TGF)-ß1 and interleukin (IL)-10 compared with CD4⁺CD25^- T cells when stimulated by plate-bound anti-CD3 and soluble anti-CD28 and/or IL-2, and secretion of TGF-ß1 (but not other cytokines), is further enhanced by costimulation via cytotoxic T lymphocyte–associated antigen (CTLA)-4. As in prior studies, we found that CD4⁺CD25⁺ T cells suppress proliferation of CD4⁺CD25^- T cells; however, we observed here that such suppression is abolished by the presence of anti–TGF-ß. In addition, we found that CD4⁺CD25⁺ T cells suppress B cell immunoglobulin production and that anti–TGF-ß again abolishes such suppression. Finally, we found that stimulated CD4⁺CD25⁺ T cells but not CD4⁺CD25^- T cells express high and persistent levels of TGF-ß1 on the cell surface. This, plus the fact that we could find no evidence that a soluble factor mediates suppression, strongly suggests that CD4⁺CD25⁺ T cells exert immunosuppression by a cell–cell interaction involving cell surface TGF-ß1.

Key Words: T lymphocytes, suppressor-effector, CD4-positive T lymphocytes, receptors, interleukin 2, transforming growth factors, autoimmune diseases

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Gondek, D. C., DeVries, V., Nowak, E. C., Lu, L.-F., Bennett, K. A., Scott, Z. A., Noelle, R. J. (2008). Transplantation Survival Is Maintained by Granzyme B+ Regulatory Cells and Adaptive Regulatory T Cells. J. Immunol. 181: 4752-4760 [Abstract] [Full Text]  
• Filippi, C. M., Juedes, A. E., Oldham, J. E., Ling, E., Togher, L., Peng, Y., Flavell, R. A., von Herrath, M. G. (2008). Transforming Growth Factor-{beta} Suppresses the Activation of CD8+ T-Cells When Naive but Promotes Their Survival and Function Once Antigen Experienced: A Two-Faced Impact on Autoimmunity. Diabetes 57: 2684-2692 [Abstract] [Full Text]  
• Trotta, R., Col, J. D., Yu, J., Ciarlariello, D., Thomas, B., Zhang, X., Allard, J. II, Wei, M., Mao, H., Byrd, J. C., Perrotti, D., Caligiuri, M. A. (2008). TGF-{beta} Utilizes SMAD3 to Inhibit CD16-Mediated IFN-{gamma} Production and Antibody-Dependent Cellular Cytotoxicity in Human NK Cells. J. Immunol. 181: 3784-3792 [Abstract] [Full Text]  
• Andersson, J., Tran, D. Q., Pesu, M., Davidson, T. S., Ramsey, H., O'Shea, J. J., Shevach, E. M. (2008). CD4+FoxP3+ regulatory T cells confer infectious tolerance in a TGF-{beta}-dependent manner. J. Exp. Med. 205: 1975-1981 [Abstract] [Full Text]  
• Marshall, N. B., Vorachek, W. R., Steppan, L. B., Mourich, D. V., Kerkvliet, N. I. (2008). Functional Characterization and Gene Expression Analysis of CD4+CD25+ Regulatory T Cells Generated in Mice Treated with 2,3,7,8-Tetrachlorodibenzo-p-Dioxin. J. Immunol. 181: 2382-2391 [Abstract] [Full Text]  
• Djoba Siawaya, J. F., Bapela, N. B., Ronacher, K., Beyers, N., van Helden, P., Walzl, G. (2008). Differential Expression of Interleukin-4 (IL-4) and IL-4{delta}2 mRNA, but Not Transforming Growth Factor Beta (TGF-{beta}), TGF-{beta}RII, Foxp3, Gamma Interferon, T-bet, or GATA-3 mRNA, in Patients with Fast and Slow Responses to Antituberculosis Treatment. CVI 15: 1165-1170 [Abstract] [Full Text]  
• Savage, N. D. L., de Boer, T., Walburg, K. V., Joosten, S. A., van Meijgaarden, K., Geluk, A., Ottenhoff, T. H. M. (2008). Human Anti-Inflammatory Macrophages Induce Foxp3+GITR+CD25+ Regulatory T Cells, Which Suppress via Membrane-Bound TGF{beta}-1. J. Immunol. 181: 2220-2226 [Abstract] [Full Text]  
• Gil-Guerrero, L., Dotor, J., Huibregtse, I. L., Casares, N., Lopez-Vazquez, A. B., Rudilla, F., Riezu-Boj, J. I., Lopez-Sagaseta, J., Hermida, J., Van Deventer, S., Bezunartea, J., Llopiz, D., Sarobe, P., Prieto, J., Borras-Cuesta, F., Lasarte, J. J. (2008). In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-{beta}1. J. Immunol. 181: 126-135 [Abstract] [Full Text]  
• Chen, M.-L., Yan, B.-S., Bando, Y., Kuchroo, V. K., Weiner, H. L. (2008). Latency-Associated Peptide Identifies a Novel CD4+CD25+ Regulatory T Cell Subset with TGF{beta}-Mediated Function and Enhanced Suppression of Experimental Autoimmune Encephalomyelitis. J. Immunol. 180: 7327-7337 [Abstract] [Full Text]  
• Takaki, H., Ichiyama, K., Koga, K., Chinen, T., Takaesu, G., Sugiyama, Y., Kato, S., Yoshimura, A., Kobayashi, T. (2008). STAT6 Inhibits TGF-{beta}1-mediated Foxp3 Induction through Direct Binding to the Foxp3 Promoter, Which Is Reverted by Retinoic Acid Receptor. J. Biol. Chem. 283: 14955-14962 [Abstract] [Full Text]  
• Perez, N., Karumuthil-Melethil, S., Li, R., Prabhakar, B. S., Holterman, M. J., Vasu, C. (2008). Preferential Costimulation by CD80 Results in IL-10-Dependent TGF-{beta}1+-Adaptive Regulatory T Cell Generation. J. Immunol. 180: 6566-6576 [Abstract] [Full Text]  
• Pina, A., Bernardino, S., Calich, V. L. G. (2008). Alveolar macrophages from susceptible mice are more competent than those of resistant mice to control initial Paracoccidioides brasiliensis infection. J. Leukoc. Biol. 83: 1088-1099 [Abstract] [Full Text]  
• Richer, M. J., Straka, N., Fang, D., Shanina, I., Horwitz, M. S. (2008). Regulatory T-Cells Protect From Type 1 Diabetes After Induction by Coxsackievirus Infection in the Context of Transforming Growth Factor-{beta}. Diabetes 57: 1302-1311 [Abstract] [Full Text]  
• Teicher, B. A, Yingling, J. M, McPherson, J. M (2008). TGF{beta} Blockade as Anticancer Therapy. aacredbook 2008: 71-81 [Abstract] [Full Text]  
• Larmonier, N., Cantrell, J., LaCasse, C., Li, G., Janikashvili, N., Situ, E., Sepassi, M., Andreansky, S., Katsanis, E. (2008). Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression. J. Leukoc. Biol. 83: 1049-1059 [Abstract] [Full Text]  
• Alisa, A., Boswell, S., Pathan, A. A., Ayaru, L., Williams, R., Behboudi, S. (2008). Human CD4+ T Cells Recognize an Epitope within {alpha}-Fetoprotein Sequence and Develop into TGF-{beta}-Producing CD4+ T Cells. J. Immunol. 180: 5109-5117 [Abstract] [Full Text]  
• Sumpter, T. L., Payne, K. K., Wilkes, D. S. (2008). Regulation of the NFAT pathway discriminates CD4+CD25+ regulatory T cells from CD4+CD25- helper T cells. J. Leukoc. Biol. 83: 708-717 [Abstract] [Full Text]  
• Asano, N., Watanabe, T., Kitani, A., Fuss, I. J., Strober, W. (2008). Notch1 Signaling and Regulatory T Cell Function. J. Immunol. 180: 2796-2804 [Abstract] [Full Text]  
• Ostad, M., Andersson, M., Gruber, A., Sundblad, A. (2008). Expansion of immunoglobulin autoreactive T-helper cells in multiple myeloma. Blood 111: 2725-2732 [Abstract] [Full Text]  
• Kashyap, M., Thornton, A. M., Norton, S. K., Barnstein, B., Macey, M., Brenzovich, J., Shevach, E., Leonard, W. J., Ryan, J. J. (2008). Cutting Edge: CD4 T Cell-Mast Cell Interactions Alter IgE Receptor Expression and Signaling. J. Immunol. 180: 2039-2043 [Abstract] [Full Text]  
• Singh, R. P., La Cava, A., Hahn, B. H. (2008). pConsensus Peptide Induces Tolerogenic CD8+ T Cells in Lupus-Prone (NZB x NZW)F1 Mice by Differentially Regulating Foxp3 and PD1 Molecules. J. Immunol. 180: 2069-2080 [Abstract] [Full Text]  
• Chen, G., Han, G., Wang, J., Wang, R., Xu, R., Shen, B., Qian, J., Li, Y. (2008). Essential roles of TGF-{beta} in anti-CD3 antibody therapy: reversal of diabetes in nonobese diabetic mice independent of Foxp3+CD4+ regulatory T cells. J. Leukoc. Biol. 83: 280-287 [Abstract] [Full Text]  
• Dittrich, A. M., Erbacher, A., Specht, S., Diesner, F., Krokowski, M., Avagyan, A., Stock, P., Ahrens, B., Hoffmann, W. H., Hoerauf, A., Hamelmann, E. (2008). Helminth Infection with Litomosoides sigmodontis Induces Regulatory T Cells and Inhibits Allergic Sensitization, Airway Inflammation, and Hyperreactivity in a Murine Asthma Model. J. Immunol. 180: 1792-1799 [Abstract] [Full Text]  
• Ruzek, M. C., Waire, J. S., Hopkins, D., LaCorcia, G., Sullivan, J., Roberts, B. L., Richards, S. M., Nahill, S. R., Williams, J. M., Scaria, A., Dzuris, J., Shankara, S., Garman, R. D. (2008). Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo. Blood 111: 1726-1734 [Abstract] [Full Text]  
• van Puijvelde, G.H.M., van Es, T., van Wanrooij, E.J.A., Habets, K.L.L., de Vos, P., van der Zee, R., van Eden, W., van Berkel, Th. J.C., Kuiper, J. (2007). Induction of Oral Tolerance to HSP60 or an HSP60-Peptide Activates T Cell Regulation and Reduces Atherosclerosis. Arterioscler. Thromb. Vasc. Bio. 27: 2677-2683 [Abstract] [Full Text]  
• Molitor-Dart, M. L., Andrassy, J., Kwun, J., Kayaoglu, H. A., Roenneburg, D. A., Haynes, L. D., Torrealba, J. R., Bobadilla, J. L., Sollinger, H. W., Knechtle, S. J., Burlingham, W. J. (2007). Developmental Exposure to Noninherited Maternal Antigens Induces CD4+ T Regulatory Cells: Relevance to Mechanism of Heart Allograft Tolerance. J. Immunol. 179: 6749-6761 [Abstract] [Full Text]  
• Reynolds, A. D., Banerjee, R., Liu, J., Gendelman, H. E., Mosley, R. L. (2007). Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J. Leukoc. Biol. 82: 1083-1094 [Abstract] [Full Text]  
• Teicher, B. A. (2007). Transforming Growth Factor-{beta} and the Immune Response to Malignant Disease. Clin. Cancer Res. 13: 6247-6251 [Abstract] [Full Text]  
• Sutmuller, R., Garritsen, A., Adema, G. J (2007). Regulatory T cells and toll-like receptors: regulating the regulators. Ann Rheum Dis 66: iii91-iii95 [Abstract] [Full Text]  
• Li, R., Perez, N., Karumuthil-Melethil, S., Prabhakar, B. S., Holterman, M. J., Vasu, C. (2007). Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25 TGF-beta1+ Adaptive Regulatory T Cells. J. Immunol. 179: 5191-5203 [Abstract] [Full Text]  
• Kang, S. G., Lim, H. W., Andrisani, O. M., Broxmeyer, H. E., Kim, C. H. (2007). Vitamin A Metabolites Induce Gut-Homing FoxP3+ Regulatory T Cells. J. Immunol. 179: 3724-3733 [Abstract] [Full Text]  
• Kapp, J. A., Honjo, K., Kapp, L. M., Goldsmith, K., Bucy, R. P. (2007). Antigen, in the Presence of TGF-beta, Induces Up-Regulation of FoxP3gfp+ in CD4+ TCR Transgenic T Cells That Mediate Linked Suppression of CD8+ T Cell Responses. J. Immunol. 179: 2105-2114 [Abstract] [Full Text]  
• Johnson, T. V., Camras, C. B., Kipnis, J. (2007). Bacterial DNA Confers Neuroprotection after Optic Nerve Injury by Suppressing CD4+CD25+ Regulatory T-Cell Activity. IOVS 48: 3441-3449 [Abstract] [Full Text]  
• Feunou, P., Vanwetswinkel, S., Gaudray, F., Goldman, M., Matthys, P., Braun, M. Y. (2007). Foxp3+CD25+ T Regulatory Cells Stimulate IFN-{gamma}-Independent CD152-Mediated Activation of Tryptophan Catabolism That Provides Dendritic Cells with Immune Regulatory Activity in Mice Unresponsive to Staphylococcal Enterotoxin B. J. Immunol. 179: 910-917 [Abstract] [Full Text]  
• Robinson, R. T., Gorham, J. D. (2007). TGF-beta1 Regulates Antigen-Specific CD4+ T Cell Responses in the Periphery. J. Immunol. 179: 71-79 [Abstract] [Full Text]  
• Xu, L., Kitani, A., Fuss, I., Strober, W. (2007). Cutting Edge: Regulatory T Cells Induce CD4+CD25-Foxp3- T Cells or Are Self-Induced to Become Th17 Cells in the Absence of Exogenous TGF-beta. J. Immunol. 178: 6725-6729 [Abstract] [Full Text]  
• Pereira, L. E., Villinger, F., Onlamoon, N., Bryan, P., Cardona, A., Pattanapanysat, K., Mori, K., Hagen, S., Picker, L., Ansari, A. A. (2007). Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys. J. Virol. 81: 4445-4456 [Abstract] [Full Text]  
• Nie, C. Q., Bernard, N. J., Schofield, L., Hansen, D. S. (2007). CD4+ CD25+ Regulatory T Cells Suppress CD4+ T-Cell Function and Inhibit the Development of Plasmodium berghei-Specific TH1 Responses Involved in Cerebral Malaria Pathogenesis. Infect. Immun. 75: 2275-2282 [Abstract] [Full Text]  
• Pop, S. M., Wong, C. P., He, Q., Wang, Y., Wallet, M. A., Goudy, K. S., Tisch, R. (2007). The Type and Frequency of Immunoregulatory CD4+ T-Cells Govern the Efficacy of Antigen-Specific Immunotherapy in Nonobese Diabetic Mice. Diabetes 56: 1395-1402 [Abstract] [Full Text]  
• Baatar, D., Olkhanud, P., Sumitomo, K., Taub, D., Gress, R., Biragyn, A. (2007). Human Peripheral Blood T Regulatory Cells (Tregs), Functionally Primed CCR4+ Tregs and Unprimed CCR4- Tregs, Regulate Effector T Cells Using FasL. J. Immunol. 178: 4891-4900 [Abstract] [Full Text]  
• Marinova, E., Han, S., Zheng, B. (2007). Germinal Center Helper T Cells Are Dual Functional Regulatory Cells with Suppressive Activity to Conventional CD4+ T Cells. J. Immunol. 178: 5010-5017 [Abstract] [Full Text]  
• You, S., Leforban, B., Garcia, C., Bach, J.-F., Bluestone, J. A., Chatenoud, L. (2007). Adaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment. Proc. Natl. Acad. Sci. USA 104: 6335-6340 [Abstract] [Full Text]  
• Gandhi, R., Anderson, D. E., Weiner, H. L. (2007). Cutting Edge: Immature Human Dendritic Cells Express Latency-Associated Peptide and Inhibit T Cell Activation in a TGF-beta-Dependent Manner. J. Immunol. 178: 4017-4021 [Abstract] [Full Text]  
• Stein-Streilein, J., Taylor, A. W. (2007). An eye's view of T regulatory cells. J. Leukoc. Biol. 81: 593-598 [Abstract] [Full Text]  
• Liu, V. C., Wong, L. Y., Jang, T., Shah, A. H., Park, I., Yang, X., Zhang, Q., Lonning, S., Teicher, B. A., Lee, C. (2007). Tumor Evasion of the Immune System by Converting CD4+CD25- T Cells into CD4+CD25+ T Regulatory Cells: Role of Tumor-Derived TGF-beta. J. Immunol. 178: 2883-2892 [Abstract] [Full Text]  
• Zeiser, R., Nguyen, V. H., Hou, J.-Z., Beilhack, A., Zambricki, E., Buess, M., Contag, C. H., Negrin, R. S. (2007). Early CD30 signaling is critical for adoptively transferred CD4+CD25+ regulatory T cells in prevention of acute graft-versus-host disease. Blood 109: 2225-2233 [Abstract] [Full Text]  
• Garin, M. I., Chu, C.-C., Golshayan, D., Cernuda-Morollon, E., Wait, R., Lechler, R. I. (2007). Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood 109: 2058-2065 [Abstract] [Full Text]  
• Marangoni, F., Trifari, S., Scaramuzza, S., Panaroni, C., Martino, S., Notarangelo, L. D., Baz, Z., Metin, A., Cattaneo, F., Villa, A., Aiuti, A., Battaglia, M., Roncarolo, M.-G., Dupre, L. (2007). WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells. J. Exp. Med. 204: 369-380 [Abstract] [Full Text]  
• Joetham, A., Takada, K., Taube, C., Miyahara, N., Matsubara, S., Koya, T., Rha, Y.-H., Dakhama, A., Gelfand, E. W. (2007). Naturally Occurring Lung CD4+CD25+ T Cell Regulation of Airway Allergic Responses Depends on IL-10 Induction of TGF-beta. J. Immunol. 178: 1433-1442 [Abstract] [Full Text]  
• May, K. F. Jr., Chang, X., Zhang, H., Lute, K. D., Zhou, P., Kocak, E., Zheng, P., Liu, Y. (2007). B7-Deficient Autoreactive T Cells Are Highly Susceptible to Suppression by CD4+CD25+ Regulatory T Cells. J. Immunol. 178: 1542-1552 [Abstract] [Full Text]  
• Nadkarni, S., Mauri, C., Ehrenstein, M. R. (2007). Anti-TNF-{alpha} therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-{beta}. J. Exp. Med. 204: 33-39 [Abstract] [Full Text]  
• Beiting, D. P., Gagliardo, L. F., Hesse, M., Bliss, S. K., Meskill, D., Appleton, J. A. (2007). Coordinated Control of Immunity to Muscle Stage Trichinella spiralis by IL-10, Regulatory T Cells, and TGF-beta. J. Immunol. 178: 1039-1047 [Abstract] [Full Text]  
• Golshayan, D., Jiang, S., Tsang, J., Garin, M. I., Mottet, C., Lechler, R. I. (2007). In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood 109: 827-835 [Abstract] [Full Text]  
• Ralainirina, N., Poli, A., Michel, T., Poos, L., Andres, E., Hentges, F., Zimmer, J. (2007). Control of NK cell functions by CD4+CD25+ regulatory T cells. J. Leukoc. Biol. 81: 144-153 [Abstract] [Full Text]  
• Bodor, J., Fehervari, Z., Diamond, B., Sakaguchi, S. (2007). Regulatory T cell-mediated suppression: potential role of ICER. J. Leukoc. Biol. 81: 161-167 [Abstract] [Full Text]  
• Venturi, G. M., Conway, R. M., Steeber, D. A., Tedder, T. F. (2007). CD25+CD4+ Regulatory T Cell Migration Requires L-Selectin Expression: L-Selectin Transcriptional Regulation Balances Constitutive Receptor Turnover. J. Immunol. 178: 291-300 [Abstract] [Full Text]  
• Keino, H, Takeuchi, M, Usui, Y, Hattori, T, Yamakawa, N, Kezuka, T, Sakai, J-I, Usui, M (2007). Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis. Br. J. Ophthalmol. 91: 105-110 [Abstract] [Full Text]  
• Sugita, S., Keino, H., Futagami, Y., Takase, H., Mochizuki, M., Stein-Streilein, J., Streilein, J. W. (2006). B7+ Iris Pigment Epithelial Cells Convert T Cells into CTLA-4+, B7-Expressing CD8+ Regulatory T Cells. IOVS 47: 5376-5384 [Abstract] [Full Text]  
• Kobie, J. J., Shah, P. R., Yang, L., Rebhahn, J. A., Fowell, D. J., Mosmann, T. R. (2006). T Regulatory and Primed Uncommitted CD4 T Cells Express CD73, Which Suppresses Effector CD4 T Cells by Converting 5'-Adenosine Monophosphate to Adenosine. J. Immunol. 177: 6780-6786 [Abstract] [Full Text]  
• Ogawa, K., Funaba, M., Chen, Y., Tsujimoto, M. (2006). Activin A Functions as a Th2 Cytokine in the Promotion of the Alternative Activation of Macrophages. J. Immunol. 177: 6787-6794 [Abstract] [Full Text]  
• Sukiennicki, T. L., Fowell, D. J. (2006). Distinct Molecular Program Imposed on CD4+ T Cell Targets by CD4+CD25+ Regulatory T Cells. J. Immunol. 177: 6952-6961 [Abstract] [Full Text]  
• Leung, S. Y., Niimi, A., Noble, A., Oates, T., Williams, A. S., Medicherla, S., Protter, A. A., Chung, K. F. (2006). Effect of Transforming Growth Factor-beta Receptor I Kinase Inhibitor 2,4-Disubstituted Pteridine (SD-208) in Chronic Allergic Airway Inflammation and Remodeling. J. Pharmacol. Exp. Ther. 319: 586-594 [Abstract] [Full Text]  
• Menoret, A., Myers, L. M., Lee, S.-J., Mittler, R. S., Rossi, R. J., Vella, A. T. (2006). TGFbeta Protein Processing and Activity through TCR Triggering of Primary CD8+ T Regulatory Cells. J. Immunol. 177: 6091-6097 [Abstract] [Full Text]  
• Kapp, J. A., Honjo, K., Kapp, L. M., Xu, X. y., Cozier, A., Bucy, R. P. (2006). TCR transgenic CD8+ T cells activated in the presence of TGF{beta} express FoxP3 and mediate linked suppression of primary immune responses and cardiac allograft rejection. Int Immunol 18: 1549-1562 [Abstract] [Full Text]  
• van Puijvelde, G.H.M., Hauer, A.D., de Vos, P., van den Heuvel, R., van Herwijnen, M.J.C., van der Zee, R., van Eden, W., van Berkel, T.J.C., Kuiper, J. (2006). Induction of Oral Tolerance to Oxidized Low-Density Lipoprotein Ameliorates Atherosclerosis. Circulation 114: 1968-1976 [Abstract] [Full Text]  
• Nemunaitis, J., Dillman, R. O., Schwarzenberger, P. O., Senzer, N., Cunningham, C., Cutler, J., Tong, A., Kumar, P., Pappen, B., Hamilton, C., DeVol, E., Maples, P. B., Liu, L., Chamberlin, T., Shawler, D. L., Fakhrai, H. (2006). Phase II Study of Belagenpumatucel-L, a Transforming Growth Factor Beta-2 Antisense Gene-Modified Allogeneic Tumor Cell Vaccine in Non-Small-Cell Lung Cancer. JCO 24: 4721-4730 [Abstract] [Full Text]  
• Grimbert, P., Bouguermouh, S., Baba, N., Nakajima, T., Allakhverdi, Z., Braun, D., Saito, H., Rubio, M., Delespesse, G., Sarfati, M. (2006). Thrombospondin/CD47 Interaction: A Pathway to Generate Regulatory T Cells from Human CD4+CD25- T Cells in Response to Inflammation. J. Immunol. 177: 3534-3541 [Abstract] [Full Text]  
• Toda, A., Piccirillo, C. A. (2006). Development and function of naturally occurring CD4+CD25+ regulatory T cells. J. Leukoc. Biol. 80: 458-470 [Abstract] [Full Text]  
• Broderick, L., Bankert, R. B. (2006). Membrane-Associated TGF-beta1 Inhibits Human Memory T Cell Signaling in Malignant and Nonmalignant Inflammatory Microenvironments.. J. Immunol. 177: 3082-3088 [Abstract] [Full Text]  
• Iezzi, G., Boni, A., Degl'Innocenti, E., Grioni, M., Bertilaccio, M. T. S., Bellone, M. (2006). Type 2 Cytotoxic T Lymphocytes Modulate the Activity of Dendritic Cells Toward Type 2 Immune Responses. J. Immunol. 177: 2131-2137 [Abstract] [Full Text]  
• Oida, T., Xu, L., Weiner, H. L., Kitani, A., Strober, W. (2006). TGF-beta-Mediated Suppression by CD4+CD25+ T Cells Is Facilitated by CTLA-4 Signaling. J. Immunol. 177: 2331-2339 [Abstract] [Full Text]  
• Beyer, M., Schultze, J. L. (2006). Regulatory T cells in cancer. Blood 108: 804-811 [Abstract] [Full Text]  
• Eksteen, B., Miles, A., Curbishley, S. M., Tselepis, C., Grant, A. J., Walker, L. S. K., Adams, D. H. (2006). Epithelial Inflammation Is Associated with CCL28 Production and the Recruitment of Regulatory T Cells Expressing CCR10. J. Immunol. 177: 593-603 [Abstract] [Full Text]  
• Wing, K., Fehervari, Z., Sakaguchi, S. (2006). Emerging possibilities in the development and function of regulatory T cells. Int Immunol 18: 991-1000 [Abstract] [Full Text]  
• Qin, H.-Y., Mukherjee, R., Lee-Chan, E., Ewen, C., Bleackley, R. C., Singh, B. (2006). A novel mechanism of regulatory T cell-mediated down-regulation of autoimmunity. Int Immunol 18: 1001-1015 [Abstract] [Full Text]  
• Dong, M., Blobe, G. C. (2006). Role of transforming growth factor-beta in hematologic malignancies. Blood 107: 4589-4596 [Abstract] [Full Text]  
• Sharabi, A., Zinger, H., Zborowsky, M., Sthoeger, Z. M., Mozes, E. (2006). A peptide based on the complementarity-determining region 1 of an autoantibody ameliorates lupus by up-regulating CD4+CD25+ cells and TGF-beta. Proc. Natl. Acad. Sci. USA 103: 8810-8815 [Abstract] [Full Text]  
• Noble, A., Giorgini, A., Leggat, J. A. (2006). Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage. Blood 107: 4475-4483 [Abstract] [Full Text]  
• Veldhoen, M., Moncrieffe, H., Hocking, R. J., Atkins, C. J., Stockinger, B. (2006). Modulation of Dendritic Cell Function by Naive and Regulatory CD4+ T Cells. J. Immunol. 176: 6202-6210 [Abstract] [Full Text]  
• Beyer, M., Kochanek, M., Giese, T., Endl, E., Weihrauch, M. R., Knolle, P. A., Classen, S., Schultze, J. L. (2006). In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma. Blood 107: 3940-3949 [Abstract] [Full Text]  
• Duchmann, R, Zeitz, M (2006). T regulatory cell suppression of colitis: the role of TGF-{beta}. Gut 55: 604-606 [Full Text]  
• Fantini, M C, Becker, C, Tubbe, I, Nikolaev, A, Lehr, H A, Galle, P, Neurath, M F (2006). Transforming growth factor {beta} induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis. Gut 55: 671-680 [Abstract] [Full Text]  
• Yang, Z.-Z., Novak, A. J., Stenson, M. J., Witzig, T. E., Ansell, S. M. (2006). Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma. Blood 107: 3639-3646 [Abstract] [Full Text]  
• Barao, I., Hanash, A. M., Hallett, W., Welniak, L. A., Sun, K., Redelman, D., Blazar, B. R., Levy, R. B., Murphy, W. J. (2006). Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells. Proc. Natl. Acad. Sci. USA 103: 5460-5465 [Abstract] [Full Text]  
• Zhang, X., Reddy, J., Ochi, H., Frenkel, D., Kuchroo, V. K., Weiner, H. L. (2006). Recovery from experimental allergic encephalomyelitis is TGF-{beta} dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells. Int Immunol 18: 495-503 [Abstract] [Full Text]  
• Kashiwada, M., Cattoretti, G., McKeag, L., Rouse, T., Showalter, B. M., Al-Alem, U., Niki, M., Pandolfi, P. P., Field, E. H., Rothman, P. B. (2006). Downstream of Tyrosine Kinases-1 and Src Homology 2-Containing Inositol 5'-Phosphatase Are Required for Regulation of CD4+CD25+ T Cell Development. J. Immunol. 176: 3958-3965 [Abstract] [Full Text]  
• Chen, C., Lee, W.-h., Zhong, L., Liu, C.-P. (2006). Regulatory T Cells Can Mediate Their Function through the Stimulation of APCs to Produce Immunosuppressive Nitric Oxide. J. Immunol. 176: 3449-3460 [Abstract] [Full Text]  
• Keino, H., Takeuchi, M., Kezuka, T., Hattori, T., Usui, M., Taguchi, O., Streilein, J. W., Stein-Streilein, J. (2006). Induction of Eye-Derived Tolerance Does Not Depend on Naturally Occurring CD4+CD25+ T Regulatory Cells.. IOVS 47: 1047-1055 [Abstract] [Full Text]  
• Alvarez, D., Swirski, F. K., Yang, T.-C., Fattouh, R., Croitoru, K., Bramson, J. L., Stampfli, M. R., Jordana, M. (2006). Inhalation Tolerance Is Induced Selectively in Thoracic Lymph Nodes but Executed Pervasively at Distant Mucosal and Nonmucosal Tissues. J. Immunol. 176: 2568-2580 [Abstract] [Full Text]  
• Azevedo, M. S. P., Yuan, L., Pouly, S., Gonzales, A. M., Jeong, K. I., Nguyen, T. V., Saif, L. J. (2006). Cytokine Responses in Gnotobiotic Pigs after Infection with Virulent or Attenuated Human Rotavirus. J. Virol. 80: 372-382 [Abstract] [Full Text]  
• Alyanakian, M.-A., Grela, F., Aumeunier, A., Chiavaroli, C., Gouarin, C., Bardel, E., Normier, G., Chatenoud, L., Thieblemont, N., Bach, J.-F. (2006). Transforming Growth Factor-{beta} and Natural Killer T-Cells Are Involved in the Protective Effect of a Bacterial Extract on Type 1 Diabetes. Diabetes 55: 179-185 [Abstract] [Full Text]  
• Sugita, S., Ng, T. F., Lucas, P. J., Gress, R. E., Streilein, J. W. (2006). B7+ Iris Pigment Epithelium Induce CD8+ T Regulatory Cells; Both Suppress CTLA-4+ T Cells. J. Immunol. 176: 118-127 [Abstract] [Full Text]  
• Choileain, N. N., MacConmara, M., Zang, Y., Murphy, T. J., Mannick, J. A., Lederer, J. A. (2006). Enhanced Regulatory T Cell Activity Is an Element of the Host Response to Injury. J. Immunol. 176: 225-236 [Abstract] [Full Text]  
• Marski, M., Kandula, S., Turner, J. R., Abraham, C. (2005). CD18 Is Required for Optimal Development and Function of CD4+CD25+ T Regulatory Cells. J. Immunol. 175: 7889-7897 [Abstract] [Full Text]  
• Endharti, A. T., Rifa', M. I, Shi, Z., Fukuoka, Y., Nakahara, Y., Kawamoto, Y., Takeda, K., Isobe, K.-i., Suzuki, H. (2005). Cutting Edge: CD8+CD122+ Regulatory T Cells Produce IL-10 to Suppress IFN-{gamma} Production and Proliferation of CD8+ T Cells. J. Immunol. 175: 7093-7097 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS