Murine vascular endothelium activates and induces the generation of allogeneic CD4+25+Foxp3+ regulatory T cells.
Unlike graft-resident donor-derived hemopoietic APCs, which decrease in number over time after transplantation, vascular endothelial cells are lifelong residents of a vascularized allograft. Endothelial cells are potent APCs for allogeneic CD8+ T lymphocytes but are unable to induce proliferation of allogeneic CD4+ T lymphocytes. Although the reason for this differential response has been poorly understood, here we report that alloantigen presentation by vascular endothelium to CD4+ T lymphocytes activates and induces CD4+25+Foxp3+ regulatory T cells, which can inhibit proliferation of alloreactive T cells both in vitro and in vivo. This process occurs independently of B7.1 costimulation but is dependent on programmed death ligand 1 (B7-H1). This finding may have important implications for tolerance induction in transplantation.
Krupnick
Alexander Sasha
AS
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gelman
Andrew E
AE
Barchet
Winfried
W
Richardson
Steve
S
Kreisel
Friederike H
FH
Turka
Laurence A
LA
Colonna
Marco
M
Patterson
G Alexander
GA
Kreisel
Daniel
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2