How they are generated 

Th3 are obtained after oral administration of antigen in vivo. In s, oral treatment with myelin basic protein (MBP) induces a significant increase in the frequency of MBP specific T cells that secret TGF-?. These Th3 cells were originally generated and identified mice orally tolerized to MBP and suppressed the induction of experimental autoimmune encephalomyelitis (EAE) by a TGF-?-dependent mechanisms.

Th3 regs are triggered in an antigen-specific fasion but suppress in an antigen-non-specific fashion. 

In vivo in the experimental allergic encephalomyelitis (EAE) model, injection of antiCD86 but not anti-CD80 inhibited the induction of oral tolerance to low does but not high does myelin basic protein (MBP). CTLA-4 stimulation has also been reported important for high dose oral tolerance. 

Th3 regs are induced by APCs via triggering by the TCR and co-stimulation by CD86. Other co-stimulatory signals may also be involved. 

DCs in the gut have unique properties and preferentially induce Th3 cells. 

Induction of Th3 cells is enhanced by the presence of TGFbeta and IL-4, although Th3 cells can be induced in IL-4 deficient mice. 

Cytokine profile

They secrete IL-10 and TGF-beta. The induction of TGF-B secreting regulatory Th3 cells might represent a novel subversion strategy employed by tumors to suppress the induction of protective tumor specific cytotoxic T lymphocyte (CTL) responses. 

Mechanism of Suppression

L-10 and TGF-? may play a role in the suppression of immune responses since Th3 cells induced in oral tolerance protecols have been associated with the induction of these cytokines.

In contrast to Th1 and Th2 cells, Th3 cells provide help for IgA production and primarily secrete TGF-beta.