title: Occurrence of autoimmunity after xenothymus transplantation in T-cell-deficient mice depends on the thymus transplant technique.
abstract: Xenothymus transplantation under the kidney capsule in athymic rodents frequently leads to multiorgan autoimmunity. Herein, we explore whether this is an intrinsic risk of xenothymus grafting or whether it depends on the transplant technique. We developed a new technique of "venous pouch" thymus grafting (heart-xenothymus) and compared this with the conventional kidney subcapsular technique (kidney-xenothymus) in a rat-into-nude-mouse model. Whereas lethal autoimmunity developed in 90% of kidney-xenothymus recipients, all heart-xenothymus grafted mice remained completely healthy. Autoimmunity in heart-xenothymus recipients was absent despite a significantly improved T-cell generation and was associated with significantly higher CD4+CD25+ T-cell frequencies and CD4+CD25+ cell Foxp3 mRNA levels than those observed in kidney-xenothymus recipients. In conclusion, we describe a novel vascular pouch technique of xenothymus transplantation that prevents the development of autoimmunity in nude mice. Our data further suggest that prevention of autoimmunity is related to a superior development of regulatory T-cells.
authors.affiliation: Laboratory of Experimental Transplantation, University of Leuven, Leuven, Belgium.
authors.forename: Timothy
authors.initials: T
authors.lastname: Devos
authors.forename: Ben
authors.initials: B
authors.lastname: Sprangers
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Shengqiao
authors.initials: S
authors.lastname: Li
authors.forename: Yehong
authors.initials: Y
authors.lastname: Yan
authors.forename: Willy
authors.initials: W
authors.lastname: Landuyt
authors.forename: Caroline
authors.initials: C
authors.lastname: Lenaerts
authors.forename: Omer
authors.initials: O
authors.lastname: Rutgeerts
authors.forename: Jozef
authors.initials: J
authors.lastname: Goebels
authors.forename: Dominique
authors.initials: D
authors.lastname: Bullens
authors.forename: Christiane
authors.initials: C
authors.lastname: De Wolf-Peeters
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: Mark
authors.initials: M
authors.lastname: Waer
authors.forename: An D
authors.initials: AD
authors.lastname: Billiau
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D008212:Lymphocyte Depletion; D051379:Mice; D051381:Rats; D013370:Subrenal Capsule Assay / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000276:immunology*