title: Isolation of human antigen-specific regulatory T cells with high suppressive function.
abstract: Adoptive transfer of regulatory T (Treg) cells could be an alternative to chronic immunosuppression for prevention of allogeneic graft rejection. While polyspecific Treg cells can prevent immune responses under lymphopenic conditions, Ag-specific Treg cells are needed to treat autoimmunity and graft rejection. Yet, reliable markers for Ag-specific Treg cells are missing. We report that latency-associated peptide (LAP) and glycoprotein A repetitions predominant (GARP) can identify human Ag-specific Treg cells. In addition, we show that the depletion of CD154(+) cells from LAP(+) or GARP(+) Treg cells increases the Treg-cell purity to over 90%, as assessed by epigenetic analysis. These Ag-specific Treg cells can be isolated magnetically and might contribute to the development of GMP-based protocols. In addition, Ag-specific Treg cells are functionally far superior to CD4(+) CD25(high) or CD4(+) CD25(high) CD127(low) Treg cells in vitro and in preventing strong alloreactions in humanized mice. They could, therefore, have a high therapeutic potential for the control of alloimmune, autoimmune, and allergic immune responses in patients.
authors.affiliation: Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Fatih
authors.initials: F
authors.lastname: Noyan
authors.forename: Young-Seon
authors.initials: YS
authors.lastname: Lee
authors.forename: Katharina
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Matthias
authors.initials: M
authors.lastname: Hardtke-Wolenski
authors.forename: Richard
authors.initials: R
authors.lastname: Taubert
authors.forename: Gregor
authors.initials: G
authors.lastname: Warnecke
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Knoefel
authors.forename: Elvira
authors.initials: E
authors.lastname: Schulde
authors.forename: Sven
authors.initials: S
authors.lastname: Olek
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Elmar
authors.initials: E
authors.lastname: Jaeckel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D002469:Cell Separation; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
chemical_list: D015703:Antigens, CD
keywords: Antigen-specific; CD154; GARP; LAP; Regulatory T (Treg) cells