title: Costimulation blockade induces foxp3(+) regulatory T cells to human embryonic stem cells.
abstract: Transplantation of human embryonic stem cells (hESCs), like other allogeneic cellular transplants, require immunomodulation or immunosuppression in order to be maintained in the recipient. Costimulation blockade applied at the time of transplantation inhibits costimulatory signals in the immunological synapse leading to a state of anergy in the donor reactive T-cell population and a state of immunological tolerance in the host. In models of solid organ transplantation, tolerance is maintained by the infiltration of Foxp3(+) regulatory T cells into the graft. In order to study if regulatory T cells could be generated to hESC transplants, costimulation blockade (CTLA4Ig, anti-CD40L, anti-LFA-1) was administered for the first week after transplantation of two different hESC lines implanted under the kidney capsule of wild-type mice. hESC transplants were maintained indefinitely, and when harvested at long-term follow-up, Foxp3(+) T-cells were found surrounding the graft, implying the maintenance of tolerance through the induction of regulatory T cells. These results imply that costimulation blockade could be a useful treatment strategy for the induction of tolerance to hESC transplants and may down-modulate immune responses locally around the graft.
authors.affiliation: Department of Emergency Medicine (Huddinge), Karolinska University Hospital , Stockholm, Sweden .
authors.forename: Karin
authors.initials: K
authors.lastname: Ljung
authors.affiliation: Department of Cardiothoracic Surgery & Anesthesiology (Solna), Karolinska University Hospital , Stockholm, Sweden .
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Simonson
authors.affiliation: Department of Molecular Medicine & Surgery, Karolinska Institute , Stockholm, Sweden .
authors.forename: Ulrika
authors.initials: U
authors.lastname: Felldin
authors.affiliation: Department of Medicine, Karolinska Institute , Stockholm, Sweden .
authors.forename: Ewa
authors.initials: E
authors.lastname: Wärdell
authors.affiliation: Department of Medical Biochemistry & Biophysics, Karolinska Institute , Stockholm, Sweden .
authors.forename: Cristian
authors.initials: C
authors.lastname: Ibarra
authors.affiliation: Department of Clinical Science, Intervention, & Technology, Karolinska Institute , Stockholm, Sweden .
authors.forename: Liselotte
authors.initials: L
authors.lastname: Antonsson
authors.affiliation: Department of Clinical Science, Intervention, & Technology, Karolinska Institute , Stockholm, Sweden .
authors.forename: Makiko
authors.initials: M
authors.lastname: Kumagai-Braesch
authors.affiliation: Department of Clinical Science, Intervention, & Technology, Karolinska Institute , Stockholm, Sweden .
authors.forename: Outi
authors.initials: O
authors.lastname: Hovatta
authors.affiliation: Department of Clinical Science, Intervention, & Technology, Karolinska Institute , Stockholm, Sweden .
authors.forename: Riina
authors.initials: R
authors.lastname: Lampela
authors.affiliation: Department of Cardiothoracic Surgery & Anesthesiology (Solna), Karolinska University Hospital , Stockholm, Sweden .
authors.forename: Karl-Henrik
authors.initials: KH
authors.lastname: Grinnemo
authors.affiliation: Department of Cardiothoracic Surgery & Anesthesiology (Solna), Karolinska University Hospital , Stockholm, Sweden .
authors.forename: Matthias
authors.initials: M
authors.lastname: Corbascio
keywords: immunology; immunotherapy; monoclonal antibodies; stem cells