Details

Autor(en) / Beteiligte

• Hu, M.
• Wang, C.
• Zhang, G. Y.
• Saito, M.
• Wang, Y. M.
• Fernandez, M. A.
• Wang, Y.
• Wu, H.
• Hawthorne, W. J.
• Jones, C.
• O'Connell, P. J.
• Sparwasser, T.
• Bishop, G. A.
• Sharland, A. F.
• Alexander, S. I.

Titel

Infiltrating Foxp3+ Regulatory T Cells From Spontaneously Tolerant Kidney Allografts Demonstrate Donor‐Specific Tolerance

Ist Teil von

• American journal of transplantation, 2013-11, Vol.13 (11), p.2819-2830

Ort / Verlag

Hoboken, NJ: Wiley

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Foxp3+ regulatory T cells (Tregs) have an essential role in immune and allograft tolerance. However, in both kidney and liver transplantation in humans, FOXP3+ Tregs have been associated with clinical rejection. Therefore, the role and function of graft infiltrating Tregs have been of great interest. In the studies outlined, we demonstrated that Foxp3+ Tregs were expanded in tolerant kidney allografts and in draining lymph nodes in the DBA/2 (H‐2d) to C57BL/6 (H‐2b) mouse spontaneous kidney allograft tolerance model. Kidney allograft tolerance was abrogated after deletion of Foxp3+ Tregs in DEpletion of REGulatory T cells (DEREG) mice. Kidney allograft infiltrating Foxp3+ Tregs (K‐Tregs) expressed elevated levels of TGF‐β, IL‐10, interferon gamma (IFN‐γ), the transcriptional repressor B lymphocyte‐induced maturation protein‐1 (Blimp‐1) and chemokine receptor 3 (Cxcr3). These K‐Tregs had the capacity to transfer dominant tolerance and demonstrate donor alloantigen‐specific tolerance to skin allografts. This study demonstrated the crucial role, potency and specificity of graft infiltrating Foxp3+ Tregs in the maintenance of spontaneously induced kidney allograft tolerance. The authors study regulatory T cells from tolerant kidney allografts and demonstrate that these cells exhibit potent and specific suppression.