| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263; and
Department of Immunology, Zymogenetics, Seattle, WA 98102
Cytokines that use the common receptor 
-chain for regulating CD8+ T cell responses to Ag include IL-2, IL-15, and the recently identified IL-21. The ability of these cytokines to regulate antitumor activity in mice has generated considerable interest in understanding their mode of action. In this study we compare the abilities of IL-2, IL-15, and IL-21 to stimulate immunity against tumors in a syngeneic thymoma model. Durable cures were only achieved in IL-21-treated mice. By monitoring both endogenous and adoptively transferred tumor Ag-specific CD8+ T cells, it was determined that IL-21 activities overlap with those of IL-2 and IL-15. Similar to IL-2, IL-21 enhanced Ag activation and clonal expansion. However, unlike IL-2 treatment, which induces activation-induced cell death, IL-21 sustained CD8+ T cell numbers long term as a result of increased survival, an effect often attributed to IL-15. These findings indicate that the mechanisms used by IL-21 to promote CD8+ T cell responses offer unique opportunities for its use in malignant diseases and infections.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  H. Sondergaard, J. M. Coquet, A. P. Uldrich, N. McLaughlin, D. I. Godfrey, P. V. Sivakumar, K. Skak, and M. J. Smyth Endogenous IL-21 Restricts CD8+ T Cell Expansion and Is not Required for Tumor Immunity J. Immunol., December 1, 2009; 183(11): 7326 - 7336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Hogg, G. C. Bowick, N. K. Herzog, M. W. Cloyd, and J. J. Endsley Induction of granulysin in CD8+ T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1 J. Leukoc. Biol., November 1, 2009; 86(5): 1191 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Thedrez, C. Harly, A. Morice, S. Salot, M. Bonneville, and E. Scotet IL-21-Mediated Potentiation of Antitumor Cytolytic and Proinflammatory Responses of Human V{gamma}9V{delta}2 T Cells for Adoptive Immunotherapy J. Immunol., March 15, 2009; 182(6): 3423 - 3431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Spolski, H.-P. Kim, W. Zhu, D. E. Levy, and W. J. Leonard IL-21 Mediates Suppressive Effects via Its Induction of IL-10 J. Immunol., March 1, 2009; 182(5): 2859 - 2867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Castermans, S. P. Tabruyn, R. Zeng, J. R. van Beijnum, C. Eppolito, W. J. Leonard, P. A. Shrikant, and A. W. Griffioen Angiostatic activity of the antitumor cytokine interleukin-21 Blood, December 15, 2008; 112(13): 4940 - 4947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kinter, E. J. Godbout, J. P. McNally, I. Sereti, G. A. Roby, M. A. O'Shea, and A. S. Fauci The Common {gamma}-Chain Cytokines IL-2, IL-7, IL-15, and IL-21 Induce the Expression of Programmed Death-1 and Its Ligands J. Immunol., November 15, 2008; 181(10): 6738 - 6746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Y. Wuest, J. Willette-Brown, S. K. Durum, and A. A. Hurwitz The influence of IL-2 family cytokines on activation and function of naturally occurring regulatory T cells J. Leukoc. Biol., October 1, 2008; 84(4): 973 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ansen, M. O. Butler, A. Berezovskaya, A. P. Murray, K. Stevenson, L. M. Nadler, and N. Hirano Dissociation of Its Opposing Immunologic Effects Is Critical for the Optimization of Antitumor CD8+ T-Cell Responses Induced by Interleukin 21 Clin. Cancer Res., October 1, 2008; 14(19): 6125 - 6136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kasprzycka, Q. Zhang, A. Witkiewicz, M. Marzec, M. Potoczek, X. Liu, H. Y. Wang, M. Milone, S. Basu, J. Mauger, et al. {gamma}c-Signaling Cytokines Induce a Regulatory T Cell Phenotype in Malignant CD4+ T Lymphocytes J. Immunol., August 15, 2008; 181(4): 2506 - 2512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ferrari-Lacraz, R. Chicheportiche, G. Schneiter, N. Molnarfi, J. Villard, and J.-M. Dayer IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes Int. Immunol., August 1, 2008; 20(8): 1009 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Halwani, J. D. Boyer, B. Yassine-Diab, E. K. Haddad, T. M. Robinson, S. Kumar, R. Parkinson, L. Wu, M. K. Sidhu, R. Phillipson-Weiner, et al. Therapeutic Vaccination with Simian Immunodeficiency Virus (SIV)-DNA+IL-12 or IL-15 Induces Distinct CD8 Memory Subsets in SIV-Infected Macaques J. Immunol., June 15, 2008; 180(12): 7969 - 7979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iuchi, S. Teitz-Tennenbaum, J. Huang, B. G. Redman, S. D. Hughes, M. Li, G. Jiang, A. E. Chang, and Q. Li Interleukin-21 Augments the Efficacy of T-Cell Therapy by Eliciting Concurrent Cellular and Humoral Responses Cancer Res., June 1, 2008; 68(11): 4431 - 4441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Thompson, B. D. Curti, B. G. Redman, S. Bhatia, J. S. Weber, S. S. Agarwala, E. L. Sievers, S. D. Hughes, T. A. DeVries, and D. F. Hausman Phase I Study of Recombinant Interleukin-21 in Patients With Metastatic Melanoma and Renal Cell Carcinoma J. Clin. Oncol., April 20, 2008; 26(12): 2034 - 2039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Smyth, M. W.L. Teng, J. Sharkey, J. A. Westwood, N. M. Haynes, H. Yagita, K. Takeda, P. V. Sivakumar, and M. H. Kershaw Interleukin 21 Enhances Antibody-Mediated Tumor Rejection Cancer Res., April 15, 2008; 68(8): 3019 - 3025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Marzec, K. Halasa, M. Kasprzycka, M. Wysocka, X. Liu, J. W. Tobias, D. Baldwin, Q. Zhang, N. Odum, A. H. Rook, et al. Differential Effects of Interleukin-2 and Interleukin-15 versus Interleukin-21 on CD4+ Cutaneous T-Cell Lymphoma Cells Cancer Res., February 15, 2008; 68(4): 1083 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. D. Davis, K. Skak, M. J. Smyth, P. E.G. Kristjansen, D. M. Miller, and P. V. Sivakumar Interleukin-21 Signaling: Functions in Cancer and Autoimmunity Clin. Cancer Res., December 1, 2007; 13(23): 6926 - 6932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liu, G. Lizee, Y. Lou, C. Liu, W. W. Overwijk, G. Wang, and P. Hwu IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells Int. Immunol., October 1, 2007; 19(10): 1213 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Onoda, M. Rahman, H. Nara, A. Araki, K. Makabe, K. Tsumoto, I. Kumagai, T. Kudo, N. Ishii, N. Tanaka, et al. Human CD4+ central and effector memory T cells produce IL-21: effect on cytokine-driven proliferation of CD4+ T cell subsets Int. Immunol., October 1, 2007; 19(10): 1191 - 1199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Barker, J. G. Parvani, D. Meyer, A. S. Hey, K. Skak, and N. L. Letvin IL-21 Induces Apoptosis of Antigen-Specific CD8+ T Lymphocytes J. Immunol., September 15, 2007; 179(6): 3596 - 3603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ostiguy, E.-L. Allard, M. Marquis, J. Leignadier, and N. Labrecque IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade J. Leukoc. Biol., September 1, 2007; 82(3): 645 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Casey and M. F. Mescher IL-21 Promotes Differentiation of Naive CD8 T Cells to a Unique Effector Phenotype J. Immunol., June 15, 2007; 178(12): 7640 - 7648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. D. Davis, B. K. Skrumsager, J. Cebon, T. Nicholaou, J. W. Barlow, N. P. H. Moller, K. Skak, D. Lundsgaard, K. S. Frederiksen, P. Thygesen, et al. An Open-Label, Two-Arm, Phase I Trial of Recombinant Human Interleukin-21 in Patients with Metastatic Melanoma Clin. Cancer Res., June 15, 2007; 13(12): 3630 - 3636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. White, S. Krishnan, N. Strbo, H. Liu, M. A. Kolber, M. G. Lichtenheld, R. N. Pahwa, and S. Pahwa 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, May 1, 2007; 109(9): 3873 - 3880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Herber, T. P. Brown, S. Liang, D. A. Young, M. Collins, and K. Dunussi-Joannopoulos IL-21 Has a Pathogenic Role in a Lupus-Prone Mouse Model and Its Blockade with IL-21R.Fc Reduces Disease Progression J. Immunol., March 15, 2007; 178(6): 3822 - 3830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cappuccio, M. Elishmereni, and Z. Agur Cancer immunotherapy by interleukin-21: potential treatment strategies evaluated in a mathematical model. Cancer Res., July 15, 2006; 66(14): 7293 - 7300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Roda, R. Parihar, A. Lehman, A. Mani, S. Tridandapani, and W. E. Carson III Interleukin-21 Enhances NK Cell Activation in Response to Antibody-Coated Targets J. Immunol., July 1, 2006; 177(1): 120 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bolesta, A. Kowalczyk, A. Wierzbicki, C. Eppolito, Y. Kaneko, M. Takiguchi, L. Stamatatos, P. A. Shrikant, and D. Kozbor Increased Level and Longevity of Protective Immune Responses Induced by DNA Vaccine Expressing the HIV-1 Env Glycoprotein when Combined with IL-21 and IL-15 Gene Delivery J. Immunol., July 1, 2006; 177(1): 177 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Smyth, Y. Hayakawa, E. Cretney, N. Zerafa, P. Sivakumar, H. Yagita, and K. Takeda IL-21 Enhances Tumor-Specific CTL Induction by Anti-DR5 Antibody Therapy J. Immunol., May 15, 2006; 176(10): 6347 - 6355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. de Totero, R. Meazza, S. Zupo, G. Cutrona, S. Matis, M. Colombo, E. Balleari, I. Pierri, M. Fabbi, M. Capaia, et al. Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells Blood, May 1, 2006; 107(9): 3708 - 3715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Burgess, A. I. Marusina, I. Pathmanathan, F. Borrego, and J. E. Coligan IL-21 Down-Regulates NKG2D/DAP10 Expression on Human NK and CD8+ T Cells J. Immunol., February 1, 2006; 176(3): 1490 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Comes, O. Rosso, A. M. Orengo, E. Di Carlo, C. Sorrentino, R. Meazza, T. Piazza, B. Valzasina, P. Nanni, M. P. Colombo, et al. CD25+ Regulatory T Cell Depletion Augments Immunotherapy of Micrometastases by an IL-21-Secreting Cellular Vaccine J. Immunol., February 1, 2006; 176(3): 1750 - 1758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-X. Wang, R. Li, G. Yang, M. Lim, A. O'Hara, Y. Chu, B. A. Fox, N. P. Restifo, W. J. Urba, and H.-M. Hu Interleukin-7-Dependent Expansion and Persistence of Melanoma-Specific T Cells in Lymphodepleted Mice Lead to Tumor Regression and Editing Cancer Res., November 15, 2005; 65(22): 10569 - 10577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Takaki, Y. Hayakawa, A. Nelson, P. V. Sivakumar, S. Hughes, M. J. Smyth, and L. L. Lanier IL-21 Enhances Tumor Rejection through a NKG2D-Dependent Mechanism J. Immunol., August 15, 2005; 175(4): 2167 - 2173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, M. Bleakley, and C. Yee IL-21 Influences the Frequency, Phenotype, and Affinity of the Antigen-Specific CD8 T Cell Response J. Immunol., August 15, 2005; 175(4): 2261 - 2269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Alves, F. A. Arosa, and R. A. W. van Lier IL-21 Sustains CD28 Expression on IL-15-Activated Human Naive CD8+ T Cells J. Immunol., July 15, 2005; 175(2): 755 - 762. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
