Methods and compounds for prevention of graft rejection
AssigneeBeth Israel Hospital Association, a Massachusetts corporation
InventorsTerry B. Storm, Towia Libermann
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Abstract
Disclosed is a method of localized immunosuppression which may be used for preventing graft rejection or for preventing tissue destruction due to autoimmune disease. Also disclosed is a protein suppressor factor that is secreted by cloned anergic T-cells, blocks interleukin 2 (IL-2) stimulated T-cell proliferation, has an apparent molecular weight of between 10 and 30 kilodaltons, can be inactivated by heating to 65° C. for 15 minutes, blocks interleukin 4 (IL-4) stimulated T-cell proliferation in vitro, is non-cytotoxic to T-cells, and does not inhibit the production of IL-2 by T-cells in vitro.
Claims50
A method of inhibiting rejection of a transplanted tissue in a mammal, said method comprising the steps of
- a) introducing into a cell, either in vivo or ex vivo, DNA encoding an immunosuppressive polypeptide, and
- b) if step (a) was carried out ex vivo, transplanting said cell into said mammal
- wherein expression of said polypeptide is regulated by DNA which does not naturally regulate said expression, so that said polypeptide is expressed close enough to said transplanted tissue to inhibit rejection.
A method of inhibiting rejection of a transplanted tissue in a mammal, said method comprising the steps of
- a) introducing into a cell, either in vivo or ex vivo, DNA encoding a glycosidase, and
- b) if step (a) was carried out ex vivo, transplanting said cell into said mammal wherein expression of said glycosidase is regulated by DNA which does not naturally regulate said expression, so that said polypeptide is expressed close enough to said transplanted tissue to inhibit rejection.
A method of inhibiting a destructive autoimmune response in a mammal, said method comprising the steps of
- a) introducing into a cell, either in vivo or ex vivo, DNA encoding an immunosuppressive polypeptide, and
- b) if step (a) was carried out ex vivo, transplanting said cell into said mammal
- wherein expression of said polypeptide is regulated by DNA which does not naturally regulate said expression, so that said polypeptide is expressed close enough to the site of said destructive autoimmune response to inhibit destruction.
A substantially pure protein characterized in that
- it is secreted by cloned anergic T-cells,
- it blocks IL-2 stimulated T-cell proliferation,
- it has an apparent molecular weight of between 10 and 30 kilodaltons,
- it can be inactivated by heating to 65° C. for 15 minutes,
- it blocks IL-4 stimulated T-cell proliferation in vitro,
- it is non-cytotoxic to T-cells, and
- it does not inhibit the production of IL-2 by T-cells in vitro.
A human T-cell clone characterized in that it
- is anergic;
- is dependent on recombinant human IL-2 for growth;
- expresses cell surface CD8;
- is non-cytolytic;
- and,
- expresses Vβ11 T cell receptor.
Dependencies are inferred from the claim text.