Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells

doi:10.1084/jem.171.4.1269

This Article

	Full Text (PDF, 1026K)
	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 Smyth, M. J.
	Articles by Young, H. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Smyth, M. J.
	Articles by Young, H. A.


Social Bookmarking

	What's this?

ARTICLES

Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells

MJ Smyth, JR Ortaldo, Y Shinkai, H Yagita, M Nakata, K Okumura and HA Young
Laboratory of Experimental Immunology, National Cancer Institute- Frederick Cancer Research Facility, Maryland 21701.

Our studies have analyzed pore-forming protein (PFP) mRNA expression in resting and stimulated human peripheral blood CD3- large granular lymphocytes (LGL), CD3+ T cells, and their CD4+ or CD8+ subsets. Signals that stimulate T cells to develop cytotoxic activity (i.e., IL- 2 or OKT-3 mAb) led to the induction of PFP mRNA in T cells. The data indicated that IL-2 directly increased PFP mRNA in the CD8+ subset of T cells, in the absence of new DNA or protein synthesis. Abrogation of IL- 2-induced PFP mRNA expression and cytotoxic potential of T cells by the anti-p75 IL-2 receptor mAb suggested that low numbers of p75 IL-2 receptors on CD8+ T cells were capable of transducing signals responsible for these IL-2-induced effects. The induction of T cell PFP mRNA via CD3, using OKT-3 mAb, was less rapid but greater than that caused by IL-2; however, a combination of PMA and ionomycin, which bypasses crosslinking of the TCR/CD3 complex, could not mimic this increase in PFP mRNA levels in T cells. The role of second messenger systems in regulating PFP mRNA expression remains to be determined. In contrast, high constitutive PFP mRNA expression was observed in CD3- LGL and these mRNA levels could not be enhanced by stimulation with IL- 2. The cytotoxic potential of peripheral blood T cells and LGL induced in response to IL-2 correlated with IL-2-induced PFP mRNA levels in these cells and was consistent with PFP being one of several important molecules involved in the effector function of cytotoxic lymphocytes.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Street, S. E.A., Zerafa, N., Iezzi, M., Westwood, J. A., Stagg, J., Musiani, P., Smyth, M. J. (2007). Host Perforin Reduces Tumor Number but Does Not Increase Survival in Oncogene-Driven Mammary Adenocarcinoma. Cancer Res. 67: 5454-5460 [Abstract] [Full Text]
White, L., Krishnan, S., Strbo, N., Liu, H., Kolber, M. A., Lichtenheld, M. G., Pahwa, R. N., Pahwa, S. (2007). Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation, and proliferation in CD8 T cells of patients with human immunodeficiency virus-1 (HIV). Blood 109: 3873-3880 [Abstract] [Full Text]
Zheng, C. F., Ma, L. L., Jones, G. J., Gill, M. J., Krensky, A. M., Kubes, P., Mody, C. H. (2007). Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients. Blood 109: 2049-2057 [Abstract] [Full Text]
Kojima, H., Kanno, Y., Hase, H., Kobata, T. (2005). CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation. J. Immunol. 174: 5959-5967 [Abstract] [Full Text]
Sedelies, K. A., Sayers, T. J., Edwards, K. M., Chen, W., Pellicci, D. G., Godfrey, D. I., Trapani, J. A. (2004). Discordant Regulation of Granzyme H and Granzyme B Expression in Human Lymphocytes. J. Biol. Chem. 279: 26581-26587 [Abstract] [Full Text]
Street, S. E.A., Hayakawa, Y., Zhan, Y., Lew, A. M., MacGregor, D., Jamieson, A. M., Diefenbach, A., Yagita, H., Godfrey, D. I., Smyth, M. J. (2004). Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and {gamma}{delta} T Cells. JEM 199: 879-884 [Abstract] [Full Text]
Ma, L. L., Spurrell, J. C. L., Wang, J. F., Neely, G. G., Epelman, S., Krensky, A. M., Mody, C. H. (2002). CD8 T Cell-Mediated Killing of Cryptococcus neoformans Requires Granulysin and Is Dependent on CD4 T Cells and IL-15. J. Immunol. 169: 5787-5795 [Abstract] [Full Text]
Kogawa, K., Lee, S. M., Villanueva, J., Marmer, D., Sumegi, J., Filipovich, A. H. (2002). Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members. Blood 99: 61-66 [Abstract] [Full Text]
Lee, C.-K., Rao, D. T., Gertner, R., Gimeno, R., Frey, A. B., Levy, D. E. (2000). Distinct Requirements for IFNs and STAT1 in NK Cell Function. J. Immunol. 165: 3571-3577 [Abstract] [Full Text]
Smyth, M. J., Thia, K. Y.T., Street, S. E.A., MacGregor, D., Godfrey, D. I., Trapani, J. A. (2000). Perforin-mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma. JEM 192: 755-760 [Abstract] [Full Text]
Bruno, A. P., Lautier, D., d'Orgeix, A. d. T., Laurent, G., Quillet-Mary, A. (2000). Acute myeloblastic leukemic cells acquire cellular cytotoxicity under genotoxic stress: implication of granzyme B and perforin. Blood 96: 1914-1920 [Abstract] [Full Text]
Zhang, J., Scordi, I., Smyth, M. J., Lichtenheld, M. G. (1999). Interleukin 2 Receptor Signaling Regulates the Perforin Gene through Signal Transducer and Activator of Transcription (Stat)5 Activation of Two Enhancers. JEM 190: 1297-1308 [Abstract] [Full Text]
Yasukawa, M., Ohminami, H., Yakushijin, Y., Arai, J., Hasegawa, A., Ishida, Y., Fujita, S. (1999). Fas-Independent Cytotoxicity Mediated by Human CD4+ CTL Directed Against Herpes Simplex Virus-Infected Cells. J. Immunol. 162: 6100-6106 [Abstract] [Full Text]
Yu, C.-R., Ortaldo, J. R., Curiel, R. E., Young, H. A., Anderson, S. K., Gosselin, P. (1999). Role of a STAT Binding Site in the Regulation of the Human Perforin Promoter. J. Immunol. 162: 2785-2790 [Abstract] [Full Text]
Smyth, M. J., Trapani, J. A. (1998). The Relative Role of Lymphocyte Granule Exocytosis versus Death Receptor-Mediated Cytotoxicity in Viral Pathophysiology. J. Virol. 72: 1-9 [Full Text]
Babichuk, C. K., Bleackley, R. C. (1997). Mutational Analysis of the Murine Granzyme B Gene Promoter in Primary T Cells and a T Cell Clone. J. Biol. Chem. 272: 18564-18571 [Abstract] [Full Text]