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Science 311 (5769): 1924-1927

Copyright © 2006 by the American Association for the Advancement of Science

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*

Abstract: 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


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D. Kamimura and M. J. Bevan (2008)
J. Immunol. 181, 5433-5441
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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
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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
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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 »

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