Inhibition of cytotoxic T cell development by transforming growth factor beta and reversal by recombinant tumor necrosis factor alpha

doi:10.1084/jem.166.4.991

This Article

	Full Text (PDF, 452K)
	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 Ranges, G. E.
	Articles by Palladino, M. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Ranges, G. E.
	Articles by Palladino, M. A., Jr


Social Bookmarking

	What's this?

ARTICLES

Inhibition of cytotoxic T cell development by transforming growth factor beta and reversal by recombinant tumor necrosis factor alpha

GE Ranges, IS Figari, T Espevik and MA Palladino Jr
Department of Molecular Immunology, Genentech, Inc., South San Francisco, California 94080.

The immunoregulatory effects of transforming growth factor beta (TGF- beta) and recombinant murine tumor necrosis factor alpha (rMuTNF-alpha) on CTL generation and activity were examined. The results demonstrate that TGF-beta, in a dose-dependent manner, inhibited CTL generation but not CTL activity. The inhibitory effects were detected only when TGF- beta was added within the first 48 h of the MLC. Little activity was seen when it was added thereafter, including the addition of TGF-beta to the cytotoxicity assay. The production of TNF-alpha, which occurs during early phases of the MLC and which is inhibited in the presence of TGF-beta, appears to have an important regulatory role, as altering the levels of TNF-alpha in an MLC can significantly influence CTL development. The inhibitory effects of TGF-beta on the MLC can be significantly reversed by the addition of rMuTNF-alpha to the cultures. These results demonstrate that TGF-beta can inhibit MLC and subsequent CTL generation at early stages of the reaction, and such inhibition may involve the suppression of TNF-alpha production.
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:

Ueda, R., Fujita, M., Zhu, X., Sasaki, K., Kastenhuber, E. R., Kohanbash, G., McDonald, H. A., Harper, J., Lonning, S., Okada, H. (2009). Systemic Inhibition of Transforming Growth Factor-{beta} in Glioma-Bearing Mice Improves the Therapeutic Efficacy of Glioma-Associated Antigen Peptide Vaccines. Clin. Cancer Res. 15: 6551-6559 [Abstract] [Full Text]
Nam, J.-S., Terabe, M., Kang, M.-J., Chae, H., Voong, N., Yang, Y.-a., Laurence, A., Michalowska, A., Mamura, M., Lonning, S., Berzofsky, J. A., Wakefield, L. M. (2008). Transforming Growth Factor {beta} Subverts the Immune System into Directly Promoting Tumor Growth through Interleukin-17. Cancer Res. 68: 3915-3923 [Abstract] [Full Text]
Wrzesinski, S. H., Wan, Y. Y., Flavell, R. A. (2007). Transforming Growth Factor-{beta} and the Immune Response: Implications for Anticancer Therapy. Clin. Cancer Res. 13: 5262-5270 [Abstract] [Full Text]
Ling, K.-L., Dulphy, N., Bahl, P., Salio, M., Maskell, K., Piris, J., Warren, B. F., George, B. D., Mortensen, N. J., Cerundolo, V. (2007). Modulation of CD103 Expression on Human Colon Carcinoma-Specific CTL. J. Immunol. 178: 2908-2915 [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]
Huang, Y., Obholzer, N., Fayad, R., Qiao, L. (2005). Turning On/Off Tumor-Specific CTL Response during Progressive Tumor Growth. J. Immunol. 175: 3110-3116 [Abstract] [Full Text]
Ahmadzadeh, M., Rosenberg, S. A. (2005). TGF-{beta}1 Attenuates the Acquisition and Expression of Effector Function by Tumor Antigen-Specific Human Memory CD8 T Cells. J. Immunol. 174: 5215-5223 [Abstract] [Full Text]
Gunnlaugsdottir, B., Maggadottir, S. M., Ludviksson, B. R. (2005). Anti-CD28-induced co-stimulation and TCR avidity regulates the differential effect of TGF-{beta}1 on CD4+ and CD8+ naive human T-cells. Int Immunol 17: 35-44 [Abstract] [Full Text]
Lucas, P. J., McNeil, N., Hilgenfeld, E., Choudhury, B., Kim, S.-J., Eckhaus, M. A., Ried, T., Gress, R. E. (2004). Transforming Growth Factor-{beta} Pathway Serves as a Primary Tumor Suppressor in CD8+ T Cell Tumorigenesis. Cancer Res. 64: 6524-6529 [Abstract] [Full Text]
Suzuki, E., Kapoor, V., Cheung, H.-K., Ling, L. E., DeLong, P. A., Kaiser, L. R., Albelda, S. M. (2004). Soluble Type II Transforming Growth Factor-{beta} Receptor Inhibits Established Murine Malignant Mesothelioma Tumor Growth by Augmenting Host Antitumor Immunity. Clin. Cancer Res. 10: 5907-5918 [Abstract] [Full Text]
Oleszak, E. L., Chang, J. R., Friedman, H., Katsetos, C. D., Platsoucas, C. D. (2004). Theiler's Virus Infection: a Model for Multiple Sclerosis. Clin. Microbiol. Rev. 17: 174-207 [Abstract] [Full Text]
Ghio, M., Ottonello, L., Contini, P., Amelotti, M., Mazzei, C., Indiveri, F., Puppo, F., Dallegri, F. (2003). Transforming growth factor-{beta}1 in supernatants from stored red blood cells inhibits neutrophil locomotion. Blood 102: 1100-1107 [Abstract] [Full Text]
Igney, F. H., Krammer, P. H. (2002). Immune escape of tumors: apoptosis resistance and tumor counterattack. J. Leukoc. Biol. 71: 907-920 [Abstract] [Full Text]
Bollard, C. M., Rossig, C., Calonge, M. J., Huls, M. H., Wagner, H.-J., Massague, J., Brenner, M. K., Heslop, H. E., Rooney, C. M. (2002). Adapting a transforming growth factor beta -related tumor protection strategy to enhance antitumor immunity. Blood 99: 3179-3187 [Abstract] [Full Text]
Furukawa, Y., Libby, P., Stinn, J. L., Becker, G., Mitchell, R. N. (2002). Cold Ischemia Induces Isograft Arteriopathy, but Does Not Augment Allograft Arteriopathy in Non-Immunosuppressed Hosts. Am. J. Pathol. 160: 1077-1087 [Abstract] [Full Text]
Yamagiwa, S., Gray, J. D., Hashimoto, S., Horwitz, D. A. (2001). A Role for TGF-{{beta}} in the Generation and Expansion of CD4+CD25+ Regulatory T Cells from Human Peripheral Blood. J. Immunol. 166: 7282-7289 [Abstract] [Full Text]
Hellström, I., Ledbetter, J. A., Scholler, N., Yang, Y., Ye, Z., Goodman, G., Pullman, J., Hayden-Ledbetter, M., Hellström, K. E. (2001). CD3-mediated activation of tumor-reactive lymphocytes from patients with advanced cancer. Proc. Natl. Acad. Sci. USA 10.1073/pnas.021557498v1 [Abstract] [Full Text]
Dalyot-Herman, N., Bathe, O. F., Malek, T. R. (2000). Reversal of CD8+ T Cell Ignorance and Induction of Anti-Tumor Immunity by Peptide-Pulsed APC. J. Immunol. 165: 6731-6737 [Abstract] [Full Text]
Selmaj, K. W (2000). Tumour necrosis factor and anti-tumour necrosis factor approach to inflammatory demyelinating diseases of the central nervous system. Ann Rheum Dis 59: i94-102 [Full Text]
Poszepczynska, E., Bagot, M., Echchakir, H., Martinvalet, D., Ramez, M., Charue, D., Boumsell, L., Bensussan, A. (2000). Functional characterization of an IL-7-dependent CD4+CD8alpha alpha + Th3-type malignant cell line derived from a patient with a cutaneous T-cell lymphoma. Blood 96: 1056-1063 [Abstract] [Full Text]
Yang, B. C., Zander, D. S., Mehta, J. L. (1999). Hypoxia-Reoxygenation-Induced Apoptosis in Cultured Adult Rat Myocytes and the Protective Effect of Platelets and Transforming Growth Factor-beta 1. J. Pharmacol. Exp. Ther. 291: 733-738 [Abstract] [Full Text]
Ginkel, F. W. v., Wahl, S. M., Kearney, J. F., Kweon, M.-N., Fujihashi, K., Burrows, P. D., Kiyono, H., McGhee, J. R. (1999). Partial IgA-Deficiency with Increased Th2-Type Cytokines in TGF-{beta}1 Knockout Mice. J. Immunol. 163: 1951-1957 [Abstract] [Full Text]
Marzo, A. L., Lake, R. A., Lo, D., Sherman, L., McWilliam, A., Nelson, D., Robinson, B. W. S., Scott, B. (1999). Tumor Antigens are Constitutively Presented in the Draining Lymph Nodes. J. Immunol. 162: 5838-5845 [Abstract] [Full Text]
Pardoux, C., Ma, X., Gobert, S., Pellegrini, S., Mayeux, P., Gay, F., Trinchieri, G., Chouaib, S. (1999). Downregulation of Interleukin-12 (IL-12) Responsiveness in Human T Cells by Transforming Growth Factor-beta : Relationship With IL-12 Signaling. Blood 93: 1448-1455 [Abstract] [Full Text]
Han, S. H., Yea, S. S., Jeon, Y. J., Yang, K.-H., Kaminski, N. E. (1998). Transforming Growth Factor-Beta 1�(TGF-beta 1) Promotes IL-2 mRNA Expression Through the Up-regulation of NF-kappa B, AP-1 and NF-AT in EL4 Cells. J. Pharmacol. Exp. Ther. 287: 1105-1112 [Abstract] [Full Text]
Coste, A., Lefaucheur, J.-P., Wang, Q.-P., Lesprit, E., Poron, F., Peynegre, R., Escudier, E. (1998). Expression of the Transforming Growth Factor {beta} Isoforms in Inflammatory Cells of Nasal Polyps. Arch Otolaryngol Head Neck Surg 124: 1361-1366 [Abstract] [Full Text]
Prevost-Blondel, A., Zimmermann, C., Stemmer, C., Kulmburg, P., Rosenthal, F. M., Pircher, H. (1998). Tumor-Infiltrating Lymphocytes Exhibiting High Ex Vivo Cytolytic Activity Fail to Prevent Murine Melanoma Tumor Growth In Vivo. J. Immunol. 161: 2187-2194 [Abstract] [Full Text]
Gorham, J. D., Guler, M. L., Fenoglio, D., Gubler, U., Murphy, K. M. (1998). Low Dose TGF-{beta} Attenuates IL-12 Responsiveness in Murine Th Cells. J. Immunol. 161: 1664-1670 [Abstract] [Full Text]
Bohn, E., Schmitt, E., Bielfeldt, C., Noll, A., Schulte, R., Autenrieth, I. B. (1998). Ambiguous Role of Interleukin-12 in Yersinia enterocolitica Infection in Susceptible and Resistant Mouse Strains. Infect. Immun. 66: 2213-2220 [Abstract] [Full Text]
Ohtsuka, K., Gray, J. D., Stimmler, M. M., Toro, B., Horwitz, D. A. (1998). Decreased Production of TGF-{beta} by Lymphocytes from Patients with Systemic Lupus Erythematosus. J. Immunol. 160: 2539-2545 [Abstract] [Full Text]
Sherrington, P. D., Scott, J. L., Jin, B., Simmons, D., Dorahy, D. J., Lloyd, J., Brien, J. H., Aebersold, R. H., Adamson, J., Zuzel, M., Burns, G. F. (1997). TLiSA1 (PTA1) Activation Antigen Implicated in T Cell Differentiation and Platelet Activation Is a Member of the Immunoglobulin Superfamily Exhibiting Distinctive Regulation of Expression. J. Biol. Chem. 272: 21735-21744 [Abstract] [Full Text]
Wick, M., Dubey, P., Koeppen, H., Siegel, C. T., Fields, P. E., Chen, L., Bluestone, J. A., Schreiber, H. (1997). Antigenic Cancer Cells Grow Progressively in Immune Hosts without Evidence for T Cell Exhaustion or Systemic Anergy. JEM 186: 229-238 [Abstract] [Full Text]
Karres, I., Kremer, J.-P., Steckholzer, U., Kenney, J. S., Ertel, W. (1996). Transforming Growth Factor-{beta}1 Inhibits Synthesis of Cytokines in Endotoxin-Stimulated Human Whole Blood. Arch Surg 131: 1310-1317 [Abstract]
Kim, J. S., Yoon, S. S., Kim, Y. H., Ryu, J. S. (1996). Serial Measurement of Interleukin-6, Transforming Growth Factor-�, and S-100 Protein in Patients With Acute Stroke. Stroke 27: 1553-1557 [Abstract] [Full Text]
Barton, D. P. J., Blanchard, D. K., Duan, C., Roberts, W. S., Cavanagh, D., DeCesare, S., Djeu, J. Y. (1995). Interleukin-12 Synergizes With Interleukin-2 to Generate Lymphokine-Activated Killer Activity in Peripheral Blood Mononuclear Cells Cultured in Ovarian Cancer Ascitic Fluid. Reproductive Sciences 2: 762-771 [Abstract]
Chang, N.-S., Chang, N. S. (1995). Transforming Growth Factor-beta1 Induction of Novel Extracellular Matrix Proteins That Trigger Resistance to Tumor Necrosis Factor Cytotoxicity in Murine L929 Fibroblasts. J. Biol. Chem. 270: 7765-7772 [Abstract] [Full Text]
Del Giudice, G., Crow, M. K. (1993). Review: Role of Transforming Growth Factor Beta (TGF{beta}) in Systemic Autoimmunity. Lupus 2: 213-220 [Abstract]
Dalton, D., Pitts-Meek, S, Keshav, S, Figari, I., Bradley, A, Stewart, T. (1993). Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science 259: 1739-1742 [Abstract]
Lefer, A., Tsao, P, Aoki, N, Palladino, M. Jr (1990). Mediation of cardioprotection by transforming growth factor-beta. Science 249: 61-64 [Abstract]
Hellstrom, I., Ledbetter, J. A., Scholler, N., Yang, Y., Ye, Z., Goodman, G., Pullman, J., Hayden-Ledbetter, M., Hellstrom, K. E. (2001). CD3-mediated activation of tumor-reactive lymphocytes from patients with advanced cancer. Proc. Natl. Acad. Sci. USA 98: 6783-6788 [Abstract] [Full Text]