Isolation of human antigen-specific regulatory T cells with high suppressive function

作者：Noyan Fatih; Lee Young Seon; Zimmermann Katharina; Hardtke Wolenski Matthias; Taubert Richard; Warnecke Gregor; Knoefel Ann Kathrin; Schulde Elvira; Olek Sven; Manns Michael P; Jaeckel Elmar^*

来源：European Journal of Immunology, 2014, 44(9): 2592-2602.

DOI：10.1002/eji.201344381

• Antigen-specific
• CD154
• GARP
• LAP
• Regulatory T (Treg) cells

Adoptive transfer of regulatory T (Treg) cells could be an alternative to chronic immunosuppression for prevention of allogeneic graft rejection. While polyspecific Treg cells can prevent immune responses under lymphopenic conditions, Ag-specific Treg cells are needed to treat autoimmunity and graft rejection. Yet, reliable markers for Ag-specific Treg cells are missing. We report that latency-associated peptide (LAP) and glycoprotein A repetitions predominant (GARP) can identify human Ag-specific Treg cells. In addition, we show that the depletion of CD154(+) cells from LAP(+) or GARP(+) Treg cells increases the Treg-cell purity to over 90%, as assessed by epigenetic analysis. These Ag-specific Treg cells can be isolated magnetically and might contribute to the development of GMP-based protocols. In addition, Ag-specific Treg cells are functionally far superior to CD4(+) CD25(high) or CD4(+)CD25(high)CD127(low) Treg cells in vitro and in preventing strong alloreactions in humanized mice. They could, therefore, have a high therapeutic potential for the control of alloimmune, autoimmune, and allergic immune responses in

• 出版日期2014-9