Presence of functional mouse regulatory CD4+CD25+T cells in xenogeneic neonatal porcine thymus-grafted athymic mice.
Xenotransplantation with porcine thymus is emerging as a possible means to reconstitute host cellular immunity and to induce immune tolerance in rodents and large animals. However, the presence of regulatory T cells (Treg cells) in this model needs to be determined. We herein demonstrated that efficient repopulation of mouse CD4+CD25+Treg cells was achieved in Balb/c nude mice by grafting neonatal porcine thymic tissue (NP THY). Mouse CD4+CD25+T cells expressed normal levels of Foxp3 in NP THY-grafted nude mice. Furthermore, these CD4+CD25+Treg cells showed significant inhibitory effects on the cell proliferation or interleukin-2 products of syngeneic T cells to alloantigens, Con A or a peptide antigen, although the potent immunosuppressive function might be lower than CD4+CD25+Treg cells in Balb/c mice. CD4+CD25+T cells in NP THY-grafted nude mice showed significantly stronger inhibition on the response to donor porcine antigens of CD4+CD25(-)T cells than CD4+CD25+Treg cells in Balb/c mice. Both CD4+CD25+Treg cells in NP THY-grafted nude and Balb/c mice prevented the development of autoimmune disease mediated by syngeneic CD4+CD25(-)T cells in a similar efficient way in the secondary recipients. These findings provide evidence for the potential involvement of CD4+CD25+Treg cells in keeping self-tolerance and transplant tolerance in this xeno-thymus transplantation model.
Sun
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Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zhao
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Wang
H
H
Sun
L
L
Yi
H
H
Zhao
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Y
D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013552:Swine; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit