Interleukin 7 receptor alpha as a potential therapeutic target in transplantation.
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.
Racapé
Maud
M
Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 643, Nantes, France.
Vanhove
Bernard
B
Soulillou
Jean-Paul
JP
Brouard
Sophie
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit