Regulatory T cells in the induction and maintenance of peripheral transplantation tolerance.
It is now possible to induce donor-specific transplantation tolerance in adult rodents using non-depleting monoclonal antibodies against T cell co-receptor and co-stimulation molecules or by immunisation with tolerogenic antigen-presenting cells. It is a common finding of all these models of peripheral tolerance, as well as of various mouse models of autoimmune disease, that regulatory CD4(+) T cells are the principal mediators. There are currently no specific markers for regulatory T cells, but in some autoimmune models their activity has been associated with the expression of activation markers such as CD25 and CTLA4, or anti-inflammatory cytokines such as IL-10 and TGF-beta. CD4(+)CD25(+) T cells from both naïve and tolerised donors are able to transfer tolerance to grafts in lymphopenic recipients, and this may be directly applicable to bone-marrow transplantation. The challenge is now to understand the biological principles that allow such immune re-programming so that they can be safely applied to clinical organ grafting.
Cobbold
Stephen P
SP
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, Oxfordshire, OX1 3RE, UK. stephen.cobbold@path.ox.ac.uk
Graca
Luis
L
Lin
Chun-Yen
CY
Adams
Elizabeth
E
Waldmann
Herman
H
D000818:Animals; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology / Q000276:immunology*