Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
American Association for Cancer Research

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 16 February 2006
Science 31 March 2006:
Vol. 311. no. 5769, pp. 1924 - 1927
DOI: 10.1126/science.1122927

Reports

Selective Stimulation of T Cell Subsets with Antibody-Cytokine Immune Complexes

Onur Boyman,1 Marek Kovar,1 Mark P. Rubinstein,1 Charles D. Surh,1 Jonathan Sprent1,2*

Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. Thus, the proliferation of CD8+ T cells in vivo is increased after the injection of a monoclonal antibody that is specific for IL-2 (IL-2 mAb), perhaps reflecting the removal of IL-2–dependent CD4+ T regulatory cells (T regs). Instead, we show here that IL-2 mAb augments the proliferation of CD8+ cells in mice simply by increasing the biological activity of preexisting IL-2 through the formation of immune complexes. When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ T regs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response.

1 Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.

* To whom correspondence should be addressed. E-mail: j.sprent{at}garvan.org.au

Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
PILAR is a novel modulator of human T-cell expansion.
E. Huarte, J. R. Cubillos-Ruiz, Y. C. Nesbeth, U. K. Scarlett, D. G. Martinez, X. A. Engle, W. F. Rigby, P. A. Pioli, P. M. Guyre, and J. R. Conejo-Garcia (2008)
Blood 112, 1259-1268
   Abstract »    Full Text »    PDF »
T-cell Development and Function Are Modulated by Dual Specificity Phosphatase DUSP5.
P. E. Kovanen, J. Bernard, A. Al-Shami, C. Liu, J. Bollenbacher-Reilley, L. Young, C. Pise-Masison, R. Spolski, and W. J. Leonard (2008)
J. Biol. Chem. 283, 17362-17369
   Abstract »    Full Text »    PDF »
Interleukin-13 Neutralization by Two Distinct Receptor Blocking Mechanisms Reduces Immunoglobulin E Responses and Lung Inflammation in Cynomolgus Monkeys.
M. T. Kasaian, X.-Y. Tan, M. Jin, L. Fitz, K. Marquette, N. Wood, T. A. Cook, J. Lee, A. Widom, R. Agostinelli, et al. (2008)
J. Pharmacol. Exp. Ther. 325, 882-892
   Abstract »    Full Text »    PDF »
Combination treatment with IL-2 and anti-IL-2 mAbs reduces tumor metastasis via NK cell activation.
G.-H. Jin, T. Hirano, and M. Murakami (2008)
Int. Immunol. 20, 783-789
   Abstract »    Full Text »    PDF »
IL-7/Anti-IL-7 mAb Complexes Restore T Cell Development and Induce Homeostatic T Cell Expansion without Lymphopenia.
O. Boyman, C. Ramsey, D. M. Kim, J. Sprent, and C. D. Surh (2008)
J. Immunol. 180, 7265-7275
   Abstract »    Full Text »    PDF »
Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma.
F. Buchegger, O. W. Press, A. B. Delaloye, and N. Ketterer (2008)
Oncologist 13, 657-667
   Abstract »    Full Text »    PDF »
IL-15R{alpha} chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation.
E. Mortier, T. Woo, R. Advincula, S. Gozalo, and A. Ma (2008)
J. Exp. Med. 205, 1213-1225
   Abstract »    Full Text »    PDF »
Cutting Edge: Enhanced IL-2 Signaling Can Convert Self-Specific T Cell Response from Tolerance to Autoimmunity.
J. Waithman, T. Gebhardt, G. M. Davey, W. R. Heath, and F. R. Carbone (2008)
J. Immunol. 180, 5789-5793
   Abstract »    Full Text »    PDF »
IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8+ T Cell Responses and Increases the Ratio of Effector/Memory CD8+ T Cells to Regulatory T Cells.
S. Mostbock, M. E. C. Lutsiak, D. E. Milenic, K. Baidoo, J. Schlom, and H. Sabzevari (2008)
J. Immunol. 180, 5118-5129
   Abstract »    Full Text »    PDF »
Preassociation of IL-15 with IL-15R{alpha}-IgG1-Fc Enhances Its Activity on Proliferation of NK and CD8+/CD44high T Cells and Its Antitumor Action.
S. Dubois, H. J. Patel, M. Zhang, T. A. Waldmann, and J. R. Muller (2008)
J. Immunol. 180, 2099-2106
   Abstract »    Full Text »    PDF »
Kinetic and Mechanistic Requirements for Helping CD8 T Cells.
P. Agnellini, M. Wiesel, K. Schwarz, P. Wolint, M. F. Bachmann, and A. Oxenius (2008)
J. Immunol. 180, 1517-1525
   Abstract »    Full Text »    PDF »
Control of Memory CD8+ T Cell Differentiation by CD80/CD86-CD28 Costimulation and Restoration by IL-2 during the Recall Response.
S. Fuse, W. Zhang, and E. J. Usherwood (2008)
J. Immunol. 180, 1148-1157
   Abstract »    Full Text »    PDF »
Cutting Edge: Mechanism of Enhancement of In Vivo Cytokine Effects by Anti-Cytokine Monoclonal Antibodies.
J. D. Phelan, T. Orekov, and F. D. Finkelman (2008)
J. Immunol. 180, 44-48
   Abstract »    Full Text »    PDF »
Rapid generation of a functional NK-cell compartment.
M. Prlic, D. Kamimura, and M. J. Bevan (2007)
Blood 110, 2024-2026
   Abstract »    Full Text »    PDF »
Naive CD8+ T cells differentiate into protective memory-like cells after IL-2 anti IL-2 complex treatment in vivo.
D. Kamimura and M. J. Bevan (2007)
J. Exp. Med. 204, 1803-1812
   Abstract »    Full Text »    PDF »
An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2.
J.-H. Cho, O. Boyman, H.-O. Kim, B. Hahm, M. P. Rubinstein, C. Ramsey, D. M. Kim, C. D. Surh, and J. Sprent (2007)
J. Exp. Med. 204, 1787-1801
   Abstract »    Full Text »    PDF »
Immune Complex Pathophysiology.
U. E. NYDEGGER (2007)
Ann. N.Y. Acad. Sci. 1109, 66-83
   Abstract »    Full Text »    PDF »
Frontiers in Nephrology: T Cell Memory as a Barrier to Transplant Tolerance.
A. Valujskikh and X. C. Li (2007)
J. Am. Soc. Nephrol. 18, 2252-2261
   Full Text »    PDF »
OX40-Mediated Differentiation to Effector Function Requires IL-2 Receptor Signaling but Not CD28, CD40, IL-12Rbeta2, or T-bet.
C. A. Williams, S. E. Murray, A. D. Weinberg, and D. C. Parker (2007)
J. Immunol. 178, 7694-7702
   Abstract »    Full Text »    PDF »
Neutralizing antibodies to interferon.
A. Noronha (2007)
Neurology 68, S16-S22
   Abstract »    Full Text »    PDF »
Interleukin-2 Mastering Regulation in Cancer and Autoimmunity.
E. MONTERO, L. ALONSO, R. PEREZ, and A. LAGE (2007)
Ann. N.Y. Acad. Sci. 1107, 239-250
   Abstract »    Full Text »    PDF »
Cutting Edge: A Regulatory T Cell-Dependent Novel Function of CD25 (IL-2R{alpha}) Controlling Memory CD8+ T Cell Homeostasis.
R. Sharma, L. Zheng, U. S. Deshmukh, W. N. Jarjour, S.-s. J. Sung, S. M. Fu, and S.-T. Ju (2007)
J. Immunol. 178, 1251-1255
   Abstract »    Full Text »    PDF »
Latent Virus Influences the Generation and Maintenance of CD8+ T Cell Memory.
B. S. Sheridan, K. M. Khanna, G. M. Frank, and R. L. Hendricks (2006)
J. Immunol. 177, 8356-8364
   Abstract »    Full Text »    PDF »
Time to restore individual rights for IL-2 and IL-15?.
Y. Tagaya (2006)
Blood 108, 409-410
   Full Text »    PDF »
A major histocompatibility complex class I-dependent subset of memory phenotype CD8+ cells.
O. Boyman, J.-H. Cho, J. T. Tan, C. D. Surh, and J. Sprent (2006)
J. Exp. Med. 203, 1817-1825
   Abstract »    Full Text »    PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)