T regs similar to Th1 and Th2 cells, arise from naive precursors and can be differentiated in vitro.

Effects of Cytokines

In the case of murine , it has been shown that IL-10 might act as a differentiation factor but not as a growth factor for these cells. Human CD4+ T cells primed in the presence of IL-10 and IFN-alpha differentiate into 

Culture of murine T cells precursors with TGF-B promotes the induction of .

Although there is little evidence for cytokine mediated differentiation of , TGF-B could be involved.

Effects of APCs

The question that arises is whether a distinct subtype or activation status of APCs exists, which promotes the differentiation of regulatory rather than  from naive precursors. There is a whole other set of PAMPS that will instruct DC to induce regulatory T cells. In other words, it is believed DCs take in signals (even cytokine signals) and conveys this to T cells.

Recent studies have suggested that activation of DCs that secrete IL-10, but not IL-12, can direct naive T cells to a subtype. IL-10 inhibits the stimulatory capacity of DCS through the downregulation of MHC class II molecules and the , thus preventing . APCs from the liver and Peyer’s path secrete high levels of IL-10 and selectively induce IL-10 secreting alloreactive Tr1 cells of Th2, respectively. It has also been suggested that immature DCs drive induction of human  in vitro.

Evidence also suggests that DC1, DC2 or Tr-driving DC (designated DCr) correspond to functional subtypes of DCs, activated through distinct signals from pathogen derived molecules, rather than different DC lineages in vivo.

The APCs and cells secreting the cytokines that drive the differentiation of Th1, Th2 or Tr cells are not confined to DCs because macrophages and other innate cells could also have a major role in this process.