| Interleukin 7 receptor alpha as a potential therapeutic target in transplantation. | |
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MedLine Citation:
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PMID: 19585222 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Drugs targeting memory lymphocytes may allow for a better control of rejection in transplantation, particularly in immunized patients. In this article the rationale of targeting interleukin 7 receptor alpha (IL-7Ralpha), a molecule expressed by both memory and naive T cells, is reviewed in the context of transplantation. Whereas naive T cells are partly responsible for acute rejection and are targeted by current immunosuppressive drugs that block costimulatory signals (cyclosporine A, anti-CD3 antibody, anti-CD52 antibody, anti-thymocyte globulin, etc.), memory T cells are resistant to costimulation blockade. As such, memory cells are an obstacle to experimental tolerance induction and may be involved in chronic rejection. There is thus much scientific interest in developing molecules able to target these cells. The role of the IL-7/IL-7Ralpha pathway in transplantation rejection has been suggested by the effect of an anti-IL-7 monoclonal antibody which, when associated with costimulation blockade, prolonged heart allograft survival in mice. Here the hypothesis that targeting IL-7Ralpha would preserve effector T cells that are less dependent on IL-7 for survival while sparing regulatory CD4+ CD25high IL-7Ralpha(low) T cells is discussed. An anti-IL-7Ralpha antibody could also help achieve allograft tolerance by reducing alloreactive cells. |
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Authors:
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Maud Racapé; Bernard Vanhove; Jean-Paul Soulillou; Sophie Brouard |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2009-07-08 |
Journal Detail:
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Title: Archivum immunologiae et therapiae experimentalis Volume: 57 ISSN: 1661-4917 ISO Abbreviation: Arch. Immunol. Ther. Exp. (Warsz.) Publication Date: 2009 Jul-Aug |
Date Detail:
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Created Date: 2009-07-15 Completed Date: 2009-09-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0114365 Medline TA: Arch Immunol Ther Exp (Warsz) Country: Switzerland |
Other Details:
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Languages: eng Pagination: 253-61 Citation Subset: IM |
Affiliation:
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Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 643, Nantes, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / therapeutic use* Antigens, CD4 Graft Rejection / immunology, prevention & control* Heart Transplantation Humans Immunologic Memory / drug effects Immunosuppression* Interleukin-2 Receptor alpha Subunit Interleukin-7 / immunology*, metabolism Interleukin-7 Receptor alpha Subunit / genetics, immunology*, metabolism Lymphocyte Activation / drug effects Mice Signal Transduction / drug effects T-Lymphocyte Subsets / immunology T-Lymphocytes, Regulatory / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antigens, CD4; 0/Interleukin-2 Receptor alpha Subunit; 0/Interleukin-7; 0/Interleukin-7 Receptor alpha Subunit |
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