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.

Détails

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Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_420C7F41481C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
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.
Périodique
Journal of Experimental Medicine
Auteur⸱e⸱s
Webster K.E., Walters S., Kohler R.E., Mrkvan T., Boyman O., Surh C.D., Grey S.T., Sprent J.
ISSN
1540-9538[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
206
Numéro
4
Pages
751-760
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
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.
Mots-clé
Animals, Antibodies, Monoclonal/pharmacology, CD4-Positive T-Lymphocytes/drug effects, CD4-Positive T-Lymphocytes/immunology, Cell Division, Encephalomyelitis, Autoimmune, Experimental/immunology, Genes, RAG-1, Glycoproteins/immunology, Graft Survival/immunology, Immunophenotyping, Interleukin-2/immunology, Interleukin-2/pharmacology, Interleukin-2 Receptor alpha Subunit/immunology, Islets of Langerhans Transplantation/immunology, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Peptide Fragments/immunology, T-Lymphocytes, Regulatory/drug effects, T-Lymphocytes, Regulatory/immunology, Transplantation, Homologous/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/11/2009 0:41
Dernière modification de la notice
20/08/2019 13:43
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