Normal development in porcine thymus grafts and specific tolerance of human T cells to porcine donor MHC.
The induction of T cell tolerance is likely to play an essential role in successful xenotransplantation in humans. In this study, we show that porcine thymus grafts in immunodeficient mice support normal development of polyclonal, functional human T cells. These T cells were specifically tolerant to MHC Ags of the porcine thymus donor and responded to nondonor porcine xenoantigens and alloantigens. Exogenous IL-2 did not abolish tolerance, suggesting central clonal deletion rather than anergy as the likely tolerance mechanism. Our study suggests that the thymic transplantation approach to achieving tolerance with restoration of immunocompetence may be applicable to xenotransplantation of pig tissues to humans.
Nikolic
B
B
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
Gardner
J P
JP
Scadden
D T
DT
Arn
J S
JS
Sachs
D H
DH
Sykes
M
M
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D005260:Female; D005333:Fetus; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D016031:Liver Transplantation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D013045:Species Specificity; D013552:Swine / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000276:immunology*