Figure 4.
Newly recruited CD4+ T-cell soldiers induced to be spies. Professional soldier lineage CD4+CD2−CD127hiFOXP3− T cells can fail to be activated into effector cells when they contact antigen. This figure illustrates four pathways that will be described in order from top to bottom. (1) Anergy is induced when there is no Signal 2, and these cells, when re-exposed to specific antigen with activated antigen-presenting cells (APCs), are not activated and do not proliferate or produce IL-2. This occurs in the absence of inflammation and activated APCs (pathway 1). (2) Induced T regulatory cells (iTregs) are induced by TGF-β and antigen when there is no IL-6 or IL-1β (pathway 2). These cells express FOXP3 and CD25 but can revert to effector T cells, because FOXP3 expressions are not stable. (3) In the mucosa, to induce oral tolerance, TGF-β and antigen can induce Th3 cells that can express FOXP3 (pathway 3). Th3 cells suppress by release of TGF-β. (4) Tr1 cells are induced by repeated culture with antigen and IL-10, which converts the APCs to DC-10 cells (pathway 4). They do not express FOXP3 or CD25 and suppress by release of TGF-β and IL-10.