Occurrence of autoimmunity after xenothymus transplantation in T-cell-deficient mice depends on the thymus transplant technique.
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.
Devos
Timothy
T
Laboratory of Experimental Transplantation, University of Leuven, Leuven, Belgium.
Sprangers
Ben
B
Lin
Yuan
Y
Li
Shengqiao
S
Yan
Yehong
Y
Landuyt
Willy
W
Lenaerts
Caroline
C
Rutgeerts
Omer
O
Goebels
Jozef
J
Bullens
Dominique
D
De Wolf-Peeters
Christiane
C
Mathieu
Chantal
C
Waer
Mark
M
Billiau
An D
AD
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*