Regulating regulatory T cells to achieve transplant tolerance.
BACKGROUND
Regulatory T cells (Tregs) play crucial roles in both induction and maintenance of tolerance. This active immune regulation may contribute not only to the control of immune responses to self-antigens and thereby prevent autoimmune diseases, but also the control of responses to non-self molecules in adaptive immunity. Numerous experimental and clinical studies indicate that manipulating the balance between regulatory and responder T cells is an effective strategy to control immune responsiveness after transplantation.


METHODS
Literature search was conducted using PubMed on the related subjects. Part of the material was based on the most recent work in the authors' laboratory.


RESULTS
We propose some new strategies to achieve transplant tolerance in rodent animals via manipulating Treg function, including using histone deacetylase (HDAC) inhibitor to regulate Foxp3 transcription and enhance Treg suppression, induction of Treg-sparing apoptosis via Nur77, and identification of the co-inhibitory molecule herpes virus entry mediator (HVEM) as an effector molecule for Treg function.


CONCLUSIONS
Regulation of Treg function will definitely provide us very promising tools to achieve clinical tolerance in the future.
Tao
Ran
R
Division of Transplantation Immunology, Department of Pathology and Laboratory Medicine, Joseph Stokes, Jr., Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. taor@upmc.edu
Hancock
Wayne W
WW
D000818:Animals; D017209:Apoptosis; D001324:Autoantigens; D001327:Autoimmune Diseases / Q000517:prevention & control*; D004268:DNA-Binding Proteins / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006650:Histocompatibility Testing / Q000379:methods; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008024:Ligands; D016031:Liver Transplantation / Q000379:methods*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011987:Receptors, Steroid / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D014157:Transcription Factors / Q000502:physiology; D023001:Transplantation Tolerance; D016896:Treatment Outcome
D001324:Autoantigens; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D008024:Ligands; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors