Transient Depletion of Dividing T Lymphocytes In Mice Induces the Emergence of Regulatory T cells and Dominant Tolerance to Islet Allografts - Immunologie-Immunopathologie-Immunothérapie Accéder directement au contenu
Article Dans Une Revue American Journal of Transplantation Année : 2008

Transient Depletion of Dividing T Lymphocytes In Mice Induces the Emergence of Regulatory T cells and Dominant Tolerance to Islet Allografts

Résumé

We previously showed that transient depletion of dividing T cells at the time of an allogeneic transplantation induces long‐term tolerance to the allograft. Here we investigated the role of homeostatic perturbation and regulatory T cells (Treg) in such tolerance. Transient depletion of dividing T cells was induced at the time of an allogeneic pancreatic islets graft, by administration of ganciclovir for 14 days, into diabetic transgenic mice expressing a thymidine kinase (TK) conditional suicide gene in T cells. Allograft tolerance was obtained in 63% of treated mice. It was not due to global immunosuppression, permanent deletion or anergy of donor‐alloantigens specific T cells but to a dominant tolerance process since lymphocytes from tolerant mice could transfer tolerance to naïve allografted recipients. The transient depletion of dividing T cells induces a 2‐ to 3‐fold increase in the proportion of CD4+CD25+Foxp3+ Treg, within 3 weeks that persisted only in allograft‐bearing mice but not in nongrafted mice. Tolerance with similar increased proportion of Treg cells was also obtained after a cytostatic hydroxyurea treatment in normal mice. Thus, the transient depletion of dividing T cells represents a novel means of immuno‐intervention based on disturbance of T‐cell homeostasis and subsequent increase in Treg proportion.
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Dates et versions

hal-01810695 , version 1 (08-06-2018)

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S. Giraud, B. Barrou, S Sebillaud, P. Debré, D. Klatzmann, et al.. Transient Depletion of Dividing T Lymphocytes In Mice Induces the Emergence of Regulatory T cells and Dominant Tolerance to Islet Allografts. American Journal of Transplantation, 2008, 8 (5), pp.942-953. ⟨10.1111/j.1600-6143.2008.02195.x⟩. ⟨hal-01810695⟩
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