Methods for repressing B cell autoantibody secretion and for treating autoimmune disorders by administration of hematopoietic stem cells and macrophage-colony stimulating factor
View Patent ↗The invention provides isolated regulatory immune cells as well as cell cultures and conditioned media derived therefrom. Also provided are methods of repressing B cell autoantibody production and/or secretion and methods of treating autoimmune disorders using regulatory immune cells or precursors thereto such as hematopoietic stem cells (HSC). The invention also provides methods of repressing B cell autoantibody production and/or secretion and methods of treating autoimmune disorders by administration of HSC and Macrophage-Colony Stimulating Factor (M-CSF). Further provided are methods of diagnosing in a mammalian subject a defect in regulatory cell mediated repression of autoantibody secretion by B cells.
1. A method of repressing B cell autoantibody secretion in a mammalian subject diagnosed with an autoimmune disorder, the method comprising:
administering a plurality of allogeneic hematopoietic stem cells (HSC) that can differentiate into dendritic cells and/or macrophages to the mammalian subject in an amount effective to repress B cell autoantibody secretion in the mammalian subject, and
administering to the mammalian subject an agent that activates dendritic cells and/or macrophages through a Toll Like receptor (TLR), CD40 antigen and/or a TNF receptor to secrete a soluble factor that represses B cell autoantibody secretion.
2. The method of claim 1 , wherein the plurality of HSC are isolated HSC.
3. The method of claim 1 , wherein the mammalian subject is given a bone marrow transplant, wherein the bone marrow transplant comprises the plurality of HSC.
4. The method of claim 1 , wherein the soluble factor comprises a cytokine.
5. The method of claim 1 , wherein the soluble factor comprises IL-6, TNF-α, CD40 ligand, or a combination thereof.
6. The method of claim 1 , wherein the autoreactive B cell is a plasma cell, plasmablast, marginal zone cell, B1 cell, transitional B cell and/or follicular B cell.
7. A method of treating an autoimmune disorder in a mammalian subject diagnosed with an autoimmune disorder, the method comprising:
administering allogeneic hematopoietic stem cells (HSC) that can differentiate into dendritic cells and/or macrophages to the mammalian subject in an amount effective to treat the autoimmune disorder, and
administering to the mammalian subject an agent that activates dendritic cells and/or macrophages through a Toll Like receptor (TLR), CD40 antigen and/or a TNF receptor to secrete a soluble factor that represses B cell autoantibody secretion.
8. The method of claim 7 , wherein the method further comprises administering to the mammalian subject a treatment-effective amount of a B cell depletion therapy.
9. The method of claim 7 , wherein the B cell depletion therapy is administered prior to administration of the HSC.
10. The method of claim 7 , wherein the plurality of HSC are isolated HSC.
11. The method of claim 7 , wherein the mammalian subject is given a bone marrow transplant, wherein the bone marrow transplant comprises the plurality of HSC.
12. The method of claim 7 , wherein the soluble factor comprises a cytokine.
13. The method of claim 7 , wherein the soluble factor comprises IL-6, TNF-α, CD40 ligand, or a combination thereof.
14. The method of claim 1 , wherein the mammalian subject is a human subject.
15. The method of claim 7 , wherein the mammalian subject is a human subject.
16. A method of repressing B cell autoantibody secretion in a mammalian subject diagnosed with systemic lupus erythematosis, the method comprising:
administering a plurality of allogeneic hematopoietic stem cells (HSC) that can differentiate into dendritic cells and/or macrophages to the mammalian subject in an amount effective to repress B cell autoantibody secretion in the mammalian subject.
17. The method of claim 16 , wherein the plurality of HSC are isolated HSC.
18. The method of claim 16 , wherein the mammalian subject is given a bone marrow transplant, wherein the bone marrow transplant comprises the plurality of HSC.
19. The method of claim 16 , wherein the mammalian subject is a human subject.
20. A method of treating systemic lupus erythematosis (SLE) in a mammalian subject diagnosed with SLE, the method comprising:
administering allogeneic hematopoietic stem cells (HSC) that can differentiate into dendritic cells and/or macrophages to the mammalian subject in an amount effective to treat SLE.
21. The method of claim 20 , wherein the method further comprises administering to the mammalian subject a treatment-effective amount of a B cell depletion therapy.
22. The method of claim 21 , wherein the B cell depletion therapy is administered prior to administration of the HSC.
23. The method of claim 20 , wherein the plurality of HSC are isolated HSC.
24. The method of claim 20 , wherein the mammalian subject is given a bone marrow transplant, wherein the bone marrow transplant comprises the plurality of ENC.
25. The method of claim 20 , wherein the mammalian subject is a human subject.