Allogeneic and xenogeneic transplantation

Patent Number: 6911220

This patent is for a very interesting idea. The induction of tolerance by ablating recipient T cells and recipient thymus, introducting a donor fetal or neonatal thymus, and allowing recipient T cells to mature with the donor thymus. This is based on the whole concept of inducing negative selection so that the recipient T cells will not kill the donor graft...but instead recognize it as self.

This concept is definately worthy of further pursuit, although at present seems very far in the future.

The inventor is one of the thought-leaders of transplantation and xenotransplantation.

The patent independent claims are below:

A method of restoring or promoting the thymus-dependent ability for T cell progenitors to develop into mature functional T cells in a primate recipient which is capable of producing T cell progenitors, wherein thymic function is essentially absent in the recipient, the method comprising inactivating mature recipient T cells and introducing into said primate recipient fetal or neonatal thymic tissue from a donor animal of a different species, so that recipient T cells can mature in said implanted donor thymic tissue.

A method of inducing tolerance in a recipient primate of a first species to a graft obtained from a donor animal of a second discordant species, said method comprising prior to or simultaneous with transplantation of said graft, introducing into said recipient, fetal or neonatal thymic tissue from the second species; and inactivating mature recipient T cells; and implanting said graft in said recipient, wherein at least one major histocompatibility locus of the donor of the thymic tissue and the donor of the graft are genetically matched; and wherein thymic function is essentially absent in the recipient.

A method of providing mature recipient T cells in a primate recipient, wherein thymic function is essentially absent in the recipient, comprising inactivating mature recipient T calls and introducing into the primate recipient fetal or neonatal swine donor thymic tissue, so that recipient T cells can mature in said introduced swine donor thymic tissue.

A method of providing mature swine donor T cells to a primate recipient which is unable to produce a normal number of mature T cells, comprising inactivating NK cells of the recipient; inactivating mature recipient T cells; introducing into said primate recipient a composition comprising swine xenogeneic donor hematopoietic stem cells, and introducing fetal or neonatal donor thymic tissue, wherein at least one major histocompatibility locus of the swine hematopoietic cells and the donor thymic tissue are genetically matched; so that said swine donor hematopoietic stem cells can mature in the donor thymus.

A method of promoting the acceptance in a recipient primate of a first species to a graft obtained from a donor animal of a second discordant species, said method comprising prior to or simultaneous with transplantation of said graft, introducing into said recipient, fetal or neonatal thymic tissue from the second species; and inactivating mature recipient T cells, implanting said graft in said recipient, wherein at least one major histocompatibility locus of the donor of the thymic tissue and the donor of the graft are genetically matched; and wherein thymic function is essentially absent in the recipient.

View this patent on the USPTO website.