Autocrine growth and tumorigenicity of interleukin 2-dependent helper T cells transfected with IL-2 gene

doi:10.1084/jem.169.1.13

This Article

	Full Text (PDF, 813K)
	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 Karasuyama, H.
	Articles by Tada, T.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Karasuyama, H.
	Articles by Tada, T.


Social Bookmarking

	What's this?

ARTICLES

Autocrine growth and tumorigenicity of interleukin 2-dependent helper T cells transfected with IL-2 gene

H Karasuyama, N Tohyama and T Tada
Department of Immunology, Faculty of Medicine, University of Tokyo, Japan.

We introduced a mouse IL-2 cDNA expression vector into an IL-2- dependent mouse helper T cell line HT-2. Transfected cells secreted substantial amounts of IL-2, to which they themselves responded by proliferating without further requirement for exogenous IL-2. The proliferation was a direct function of the cell density and was inhibitable by antibodies against IL-2 or IL-2-R, indicating the autocrine nature of the proliferation. Those producing higher amounts of IL-2 were found to be tumorigenic when inoculated into nude mice. The latency period of tumor development correlated inversely with the level of IL-2 secreted. Tumor cells proliferated in vitro in an IL-2 autocrine fashion indistinguishable from that of the inoculated cells. We thus provide evidence that the aberrant activation of the IL-2 autocrine circuit can lead T cells to malignant transformation.
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:

Love, T. M., de Jesus, R., Kean, J. A., Sheng, Q., Leger, A., Schaffhausen, B. (2005). Activation of CREB/ATF Sites by Polyomavirus Large T Antigen. J. Virol. 79: 4180-4190 [Abstract] [Full Text]
De Giovanni, C., Nicoletti, G., Landuzzi, L., Astolfi, A., Croci, S., Comes, A., Ferrini, S., Meazza, R., Iezzi, M., Di Carlo, E., Musiani, P., Cavallo, F., Nanni, P., Lollini, P.-L. (2004). Immunoprevention of HER-2/neu Transgenic Mammary Carcinoma through an Interleukin 12-Engineered Allogeneic Cell Vaccine. Cancer Res. 64: 4001-4009 [Abstract] [Full Text]
Khayyamian, S., Hutloff, A., Buchner, K., Grafe, M., Henn, V., Kroczek, R. A., Mages, H. W. (2002). ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells. Proc. Natl. Acad. Sci. USA 99: 6198-6203 [Abstract] [Full Text]
Yasui, T., Muraoka, M., Takaoka-Shichijo, Y., Ishida, I., Takegahara, N., Uchida, J., Kumanogoh, A., Suematsu, S., Suzuki, M., Kikutani, H. (2002). Dissection of B cell differentiation during primary immune responses in mice with altered CD40 signals. Int Immunol 14: 319-329 [Abstract] [Full Text]
Angelo, L. S., Talpaz, M., Kurzrock, R. (2002). Autocrine Interleukin-6 Production in Renal Cell Carcinoma: Evidence for the Involvement of p53. Cancer Res. 62: 932-940 [Abstract] [Full Text]
Tanaka, R., Yoshida, A., Murakami, T., Baba, E., Lichtenfeld, J., Omori, T., Kimura, T., Tsurutani, N., Fujii, N., Wang, Z.-X., Peiper, S. C., Yamamoto, N., Tanaka, Y. (2001). Unique Monoclonal Antibody Recognizing the Third Extracellular Loop of CXCR4 Induces Lymphocyte Agglutination and Enhances Human Immunodeficiency Virus Type 1-Mediated Syncytium Formation and Productive Infection. J. Virol. 75: 11534-11543 [Abstract] [Full Text]
Raju, K., Rabinovich, B. A., Radvanyi, L. G., Spaner, D., Miller, R. G. (2001). A central role for IL-2 in fate determination of mature T cells--I: role in determining the Th1/Th2 profile in primary T cell cultures. Int Immunol 13: 1453-1459 [Abstract] [Full Text]
Liu, K., Rosenberg, S. A. (2001). Transduction of an IL-2 Gene into Human Melanoma-Reactive Lymphocytes Results in Their Continued Growth in the Absence of Exogenous IL-2 and Maintenance of Specific Antitumor Activity. J. Immunol. 167: 6356-6365 [Abstract] [Full Text]
Rabinovich, B. A., Shannon, J., Su, R.-C., Miller, R. G. (2000). Stress Renders T Cell Blasts Sensitive to Killing by Activated Syngeneic NK Cells. J. Immunol. 165: 2390-2397 [Abstract] [Full Text]
Kusakabe, K.-i., Xin, K.-Q., Katoh, H., Sumino, K., Hagiwara, E., Kawamoto, S., Okuda, K., Miyagi, Y., Aoki, I., Nishioka, K., Klinman, D., Okuda, K. (2000). The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine. J. Immunol. 164: 3102-3111 [Abstract] [Full Text]
Su, R.-C., Kung, S. K.-P., Silver, E. T., Lemieux, S., Kane, K. P., Miller, R. G. (1999). Ly-49CB6 NK Inhibitory Receptor Recognizes Peptide-Receptive H-2Kb 1. J. Immunol. 163: 5319-5330 [Abstract] [Full Text]
Spaner, D., Sheng-Tanner, X., Raju, K., Rabinovich, B., Messner, H., Miller, R. G. (1999). Long-term persistence of IL-2-unresponsive allogeneic T cells in sublethally irradiated SCID mice. Int Immunol 11: 1601-1614 [Abstract] [Full Text]
Kung, S. K. P., Su, R.-C., Shannon, J., Miller, R. G. (1999). The NKR-P1B Gene Product Is an Inhibitory Receptor on SJL/J NK Cells. J. Immunol. 162: 5876-5887 [Abstract] [Full Text]
Spaner, D., Raju, K., Rabinovich, B., Miller, R. G. (1999). A Role for Perforin in Activation-Induced T Cell Death In Vivo: Increased Expansion of Allogeneic Perforin-Deficient T Cells in SCID mice. J. Immunol. 162: 1192-1199 [Abstract] [Full Text]
Su, R.-C., Kung, S. K. P., Gariepy, J., Barber, B. H., Miller, R. G. (1998). NK Cells Can Recognize Different Forms of Class I MHC. J. Immunol. 161: 755-766 [Abstract] [Full Text]
Sundback, J., Nakamura, M. C., Waldenstrom, M., Niemi, E. C., Seaman, W. E., Ryan, J. C., Karre, K. (1998). The {alpha}2 Domain of H-2Dd Restricts the Allelic Specificity of the Murine NK Cell Inhibitory Receptor Ly-49A. J. Immunol. 160: 5971-5978 [Abstract] [Full Text]
Kung, S. K. P., Su, R.-C., Graham, J. J. K., Chamberlain, J. W., Miller, R. G. (1998). NK Cells from Human MHC Class I (HLA-B) Transgenic Mice Do Not Mediate Hybrid Resistance Killing Against Parental Nontransgenic cells. J. Immunol. 160: 674-680 [Abstract] [Full Text]
Dorner, B., Muller, S., Entschladen, F., Schroder, J. M., Franke, P., Kraft, R., Friedl, P., Clark-Lewis, I., Kroczek, R. A. (1997). Purification, Structural Analysis, and Function of Natural ATAC, a Cytokine Secreted by CD8+ T Cells. J. Biol. Chem. 272: 8817-8823 [Abstract] [Full Text]
Hassuneh, M. R., Nagarkatti, P. S., Nagarkatti, M. (1997). Evidence for the Participation of Interleukin-2 (IL-2) and IL-4 in the Regulation of Autonomous Growth and Tumorigenesis of Transformed Cells of Lymphoid Origin. Blood 89: 610-620 [Abstract] [Full Text]
Liao, K., Lane, M. D. (1995). The Blockade of Preadipocyte Differentiation by Protein-tyrosine Phosphatase HA2 Is Reversed by Vanadate. J. Biol. Chem. 270: 12123-12132 [Abstract] [Full Text]
Toyama-Sorimachi, N., Sorimachi, H., Tobita, Y., Kitamura, F., Yagita, H., Suzuki, K., Miyasaka, M. (1995). A Novel Ligand for CD44 Is Serglycin, a Hematopoietic Cell Lineage-specific Proteoglycan. J. Biol. Chem. 270: 7437-7444 [Abstract] [Full Text]
Lin, J., Wu, X., Chen, J., Chang, A., Levine, A.J. (1994). Functions of the p53 Protein in Growth Regulation and Tumor Suppression. Cold Spring Harb Symp Quant Biol 59: 215-223 [Abstract]
Lin, W., Desiderio, S (1993). Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation. Science 260: 953-959 [Abstract]
Lin, F T, Lane, M D (1992). Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes.. Genes Dev. 6: 533-544 [Abstract]
Baker, S., Markowitz, S, Fearon, E., Willson, J., Vogelstein, B (1990). Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249: 912-915 [Abstract]