In vitro expanded alloantigen-specific CD4+CD25+ regulatory T cell treatment for the induction of donor-specific transplantation tolerance.
The key goal in clinical transplantation is the induction of donor-specific transplantation tolerance to minimise the morbidity and mortality associated with long-term immunosuppression. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) expressing forkhead transcript factor FoxP3 play a crucial role in the prevention of autoimmunity, and appear to mediate transplantation tolerance, and these cells can have indirect allospecificity for donor antigens. Here we show that self-reactive human CD4(+)CD25(+) Tregs can be subverted into allopeptide-specific cells in vitro and be expanded to large cell numbers, and that similar in vitro expanded murine CD4(+)CD25(+) Tregs with indirect allospecificity were capable of inducing donor-specific experimental transplantation tolerance. These data provide a platform for clinical studies using CD4(+)CD25(+) Tregs with indirect allospecificity as potential reagents for the induction of donor-specific transplantation tolerance.
Jiang
Shuiping
S
Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom. shuiping.jiang@kcl.ac.uk
Golshayan
Dela
D
Tsang
Julia
J
Lombardi
Giovanna
G
Lechler
Robert I
RI
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D006183:H-2 Antigens; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens; D010446:Peptide Fragments