Table 1.
Experimental approaches to the extrathymic generation of (adaptive) regulatory T cells.
| approach | references |
|---|---|
| (1) oral tolerance induction with MBP | Chen et al. (1994) |
| (2) ex vivo stimulation in the presence of IL-10 | Groux et al. (1997) |
| (3) stimulation with immature, cytokine modified or specialized DC subsets | Jonuleit et al. (2000), Levings et al. (2004), Sato et al. (2003) and Wakkach et al. (2003) |
| (4) ex vivo treatment with the pharmacological immunosuppressants vitamin D3 and dexamethasone | Barrat et al. (2002) and Vieira et al. (2004) |
| (5) ex vivo triggering of specific molecules: CD2, CD46 and Notch-1 | Hoyne et al. (2001), Kemper et al. (2003), Vigouroux et al. (2003) and Wakkach et al. (2001) |
| (6) infection with particular bacteria or parasites | McGuirk et al. (2002) and Zaccone et al. (2003) |
| (7) ex vivo treatment with TGF-β | Chen et al. (2003) |
| (8) low-zone tolerance induction by systemic administration of minute quantities of antigenic peptide | Apostolou & Von Boehmer (2004) |
A large number of experimental approaches have been shown to induce regulatory cells outside of the thymus. They may take the form of ex vivo treatment (e.g. the addition of specific cytokines or pharmacological compounds in vitro) or in vivo induction (e.g. oral tolerance). The relationship among these various regulatory cell types is still largely unclear as is their relationship to thymically generated CD25+CD4+ TR cells, though the approaches (7) and (8) listed below have resulted in the production of Foxp3+ cells. The ‘tailor-made’ generation of such regulatory cells provides hope for a potent cell-based therapy.