Compositions and methods for repressing B cell autoantibody secretion and for treating autoimmune disorders
AssigneeThe University of North Carolina at Chapel Hill
InventorsBarbara Vilen, Michelle Kilmon, Jennifer Rutan
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Abstract
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. Further provided are methods of diagnosing in a mammalian subject a defect in regulatory cell mediated repression of autoantibody secretion by B cells.
Claims38
A method of repressing B cell autoantibody secretion in a mammalian subject in need thereof, the method comprising administering a plurality of 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.
A method of repressing B cell autoantibody secretion in a mammalian subject in need thereof, the method comprising:
- culturing a plurality of hematopoietic stem cells (HSC) under conditions sufficient for the HSC to differentiate into dendritic cells and/or macrophages;
- and
- administering a plurality of the dendritic cells and/or macrophages to the mammalian subject in an amount effective to repress B cell autoantibody secretion in the mammalian subject.
14-21. (canceled)
A method of treating an autoimmune disorder in a mammalian subject in need thereof, the method comprising administering 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.
23-37. (canceled)
A method of treating an autoimmune disorder in a mammalian subject in need thereof, the method comprising:
- culturing a plurality of hematopoietic stem cells (HSC) under conditions sufficient for the HSC to differentiate into dendritic cells and/or macrophages;
- and
- administering a plurality of the dendritic cells and/or macrophages to the mammalian subject in an amount effective to treat the autoimmune disorder.
39-50. (canceled)
An isolated cell selected from the group consisting of:
- (a) an isolated dendritic cell, wherein the dendritic cell displays an epitope from a self antigen on the cell surface;
- and
- (b) an isolated macrophage, wherein the macrophage displays an epitope from a self antigen on the cell surface.
52-54. (canceled)
An isolated cell selected from the group consisting of:
- (a) an isolated dendritic cell, wherein the dendritic cell is activated to secrete a soluble factor that represses B cell autoantibody secretion;
- and
- (b) an isolated macrophage, wherein the macrophage is activated to secrete a soluble factor that represses B cell autoantibody secretion.
56-60. (canceled)
62-72. (canceled)
74-84. (canceled)
A method of activating a cell to produce a soluble factor that represses B cell autoantibody secretion, wherein the cell is a dendritic cell and/or macrophage, the method comprising contacting the cell with an agent that activates the cell through a Toll Like receptor (TLR), CD40 antigen and/or TNF receptor.
86-87. (canceled)
A method of repressing B cell autoantibody secretion in a mammalian subject in need thereof, the method comprising 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 in an amount effective to repress autoantibody secretion.
A method of treating an autoimmune disorder in a mammalian subject in need thereof, the method comprising 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 in an amount effective to treat the autoimmune disorder.
A method of repressing B cell autoantibody secretion in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a soluble factor comprising IL-6, TNF-α, CD40 ligand, or a combination thereof in an amount effective to repress B cell autoantibody secretion.
A method of treating an autoimmune disorder in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a soluble factor comprising IL-6, TNF-α, CD40 ligand, or a combination thereof in an amount effective to treat the autoimmune disorder.
A method of repressing B cell autoantibody secretion in a mammalian subject in need thereof, the method comprising administering GM-CSF and/or M-CSF to the mammalian subject in an amount effective to repress B cell autoantibody secretion.
93-94. (canceled)
A method of treating an autoimmune disorder in a mammalian subject in need thereof, the method comprising administering GM-CSF and/or M-CSF to the mammalian subject in an amount effective to treat the autoimmune disorder.
96-97. (canceled)
A method of diagnosing in a mammalian subject a defect in dendritic cell and/or macrophage mediated repression of autoantibody secretion by B cells, the method comprising:
- activating a dendritic cell and/or macrophage from the mammalian subject through a Toll Like receptor (TLR), CD40 antigen and/or a TNF receptor,
- detecting the production by the dendritic cell and/or macrophage of a soluble factor comprising IL-6, TNF-α, CD40 ligand, or a combination thereof that represses autoantibody secretion by B cells;
- wherein a reduction in production of the soluble factor as compared with a control cell indicates a defect in dendritic cell and/or macrophage mediated repression of autoantibody secretion in the mammalian subject.
99-100. (canceled)
Dependencies are inferred from the claim text.