Infectious tolerance and the long-term acceptance of transplanted tissue.
Short courses of antibody treatment aimed at blocking the coreceptors CD4 and CD8 and/or costimulatory molecules such as CD40L are able to bring about long-term acceptance and tolerance of allogeneic transplants. This tolerant state is operational, in that potential effector cells remain but are tightly regulated through the induction of antigen-specific CD4+ regulatory T cells (Tregs). CD4+ CD25+ FoxP3+ Tregs appear to play a prominent role, although other categories of Tregs have been documented. Transforming growth factor beta (TGFbeta) has been found to play a major role in the induction of the tolerant state with therapeutic antibodies as well as promoting the induction of FoxP3+ T cells from naïve populations. The observation that Tregs can be found in tolerated grafts has led to the idea that they may interact with the grafted tissue to establish a state of acquired privilege symmetrical with a similar privileged microenvironment around antigen-presenting cells in lymphoid tissues. Dampening of aggressive immune responses by Tregs allows antigen to persist and be presented in an innocuous way to promote tolerance in new cohorts of T cells throughout the life of the tolerated graft. Regulation may operate at many stages of an immune response, even as a censor at the terminal differentiation stages of effector function.
Waldmann
Herman
H
Sir William Dunn School of Pathology, Oxford, UK. herman.waldmann@path.ox.ac.uk
Adams
Elizabeth
E
Fairchild
Paul
P
Cobbold
Stephen
S
D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D007239:Infections / Q000276:immunology* / Q000628:therapy; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D023001:Transplantation Tolerance / Q000276:immunology*