The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online
doi:10.1084/jem.20082824
The Journal of Experimental Medicine, Vol. 206, No. 4, 751-760
The Rockefeller University Press, 0022-1007 $30.00
© Webster et al.
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BRIEF DEFINITIVE REPORT

 In vivo expansion of T reg cells with IL-2–mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression

Kylie E. Webster1, Stacey Walters1, Rachel E. Kohler1, Tomas Mrkvan1, Onur Boyman2, Charles D. Surh3, Shane T. Grey1, and Jonathan Sprent1

1 Immunology and Inflammation Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
2 Division of Immunology and Allergy, University Hospital of Lausanne, 1011 Lausanne, Switzerland
3 The Scripps Research Institute, La Jolla, CA 92037

CORRESPONDENCE Jonathan Sprent: j.sprent{at}garvan.org.au

Via a transcription factor, Foxp3, immunoregulatory CD4+CD25+ T cells (T reg cells) play an important role in suppressing the function of other T cells. Adoptively transferring high numbers of T reg cells can reduce the intensity of the immune response, thereby providing an attractive prospect for inducing tolerance. Extending our previous findings, we describe an in vivo approach for inducing rapid expansion of T reg cells by injecting mice with interleukin (IL)-2 mixed with a particular IL-2 monoclonal antibody (mAb). Injection of these IL-2–IL-2 mAb complexes for a short period of 3 d induces a marked (>10-fold) increase in T reg cell numbers in many organs, including the liver and gut as well as the spleen and lymph nodes, and a modest increase in the thymus. The expanded T reg cells survive for 1–2 wk and are highly activated and display superior suppressive function. Pretreating with the IL-2–IL-2 mAb complexes renders the mice resistant to induction of experimental autoimmune encephalomyelitis; combined with rapamycin, the complexes can also be used to treat ongoing disease. In addition, pretreating mice with the complexes induces tolerance to fully major histocompatibility complex–incompatible pancreatic islets in the absence of immunosuppression. Tolerance is robust and the majority of grafts are accepted indefinitely. The approach described for T reg cell expansion has clinical potential for treating autoimmune disease and promoting organ transplantation.

© 2009 Webster et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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