Different types of regulatory T cells

Different types of regulatory T cells. The four panels depict the four main types of regulatory T cells that have been characterized so far on the left of each panel, together with an indication of their interaction with antigen presenting cells (APC) on the right. (a) Natural regulatory T cells (Treg) are CD4+CD25+foxP3+ cells that are associated with TGF-β for their generation and some of their functions. They can down-modulate APC by CTLA4 cross-linking of CD80/86 molecules, the induction of indoleamine dioxygenase (IDO) and the catabolism of tryptophan. Th3 cells that make predominantly TGF-β may be similar to these Treg. (b) Anergic T cells are associated with T cell activation in the absence of costimulation and are hyporesponsive to antigen due to the induction of the E3-ubiquitin ligases GRAIL, Itch and cbl-b that cause degradation of the T cell receptor signalling pathway. Anergic cells may suppress by competing for IL-2 and costimulation. (c) Tr1 cells are dependent on IL-10 for their generation, and some of their suppressive functions. They can also modulate the APC via CTLA4, CD80/86 and IDO. (d) The CD8+CD28−foxP3+ suppressor T cell is also associated with an IL-10 rich environment and is able, at least in the human system, to modulate the dendritic antigen presenting cell to express the molecules ILT3 and ILT4 that present to further T cells to induce anergy and CD4+CD25+ Treg cells.

Publication

T cell tolerance induced by therapeutic antibodies. (2005) Stephen P Cobbold. Philos Trans R Soc Lond B Biol Sci. 2005 Sep 29;360(1461):1695-1705. Figure: F1. Homo sapiens

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