Antigen specific Tregs and related compositions, methods and systems
Antigen specific regulatory T cells are described and related compositions, methods and systems. Methods to generate an antigen specific anti-inflammatory regulatory T cell is provided, the method comprising contacting either a T cell or an antigen presenting cell with a zwitterionic polysaccharide conjugated to the antigen for a time and under condition to generate an antigen specific regulatory T cell that is capable of inhibiting a pro-inflammatory response against the antigen.
1. A method to generate an antigen specific anti-inflammatory regulatory T cell, the method comprising:
contacting an antigen presenting cell (APC) with a zwitterionic polysaccharide conjugated to the antigen in vitro in absence of a regulatory T cell to generate an APC presenting the antigen, and thereafter
contacting the APC presenting the antigen with the regulatory T cell in vivo to generate an antigen specific regulatory T cell capable of inhibiting a pro-inflammatory response against the antigen,
wherein the zwitterionic polysaccharide is selected from polysaccharide A (PSA) and polysaccharide B (PSB) from B. fragilis and the APC is a dendritic cell.
2. The method of claim 1 , wherein the polysaccharide is polysaccharide A (PSA) from B. fragilis.
3. The method of claim 1 , wherein the zwitterionic polysaccharide is conjugated to the antigen by inclusion of the zwitterionic polysaccharide and the antigen on or within a same vesicle.
4. The method of claim 3 , wherein the vesicle is an outer membrane vesicle (OMV).
5. The method of claim 1 , wherein the zwitterionic polysaccharide is conjugated to the antigen by physical connection.
6. The method of claim 1 , wherein the zwitterionic polysaccharide is conjugated to the antigen by direct or indirect covalent linkage.
7. The method claim 1 , wherein the pro-inflammatory response is a cell mediated inflammatory response.
8. The method claim 7 , wherein the cell mediated inflammatory response is a Th17 mediated response.
9. The method of claim 1 , wherein the pro-inflammatory response is a humoral inflammatory response.
10. The method of claim 1 , wherein the antigen is associated with a condition selected from the group consisting of rheumatoid arthritis, myocarditis, scleroderma, type l diabetes, multiple sclerosis, Crohn's disease, ulcerative colitis, Sjorgens syndrome, Hashimoto's thyroiditis, Graves Disease, autoimmune hepatitis, and myasthenia gravis.
11. The method of claim 1 , wherein the polysaccharide is polysaccharide A (PSA) from B. fragilis.
12. A method to generate an antigen specific anti-inflammatory regulatory T cell, the method comprising:
contacting an antigen presenting cell (APC) with a zwitterionic polysaccharide conjugated to the antigen in vitro in absence of a regulatory T cell to generate an APC presenting the antigen, and thereafter
contacting the APC presenting the antigen with the regulatory T cell to generate an antigen specific regulatory T cell capable of inhibiting a pro-inflammatory response against the antigen,
wherein the zwitterionic polysaccharide is selected from polysaccharide A (PSA) and polysaccharide B (PSB) from B. fragilis and the APC is a dendritic cell and
wherein the zwitterionic polysaccharide is conjugated to the antigen by direct or indirect covalent linkage.
13. The method of claim 12 , wherein the pro-inflammatory response is a cell mediated inflammatory response.
14. The method of claim 12 , wherein the pro-inflammatory response is a humoral inflammatory response.
15. The method of claim 12 , wherein the antigen is associated with a condition selected from the group consisting of rheumatoid arthritis, myocarditis, scleroderma, type I diabetes, multiple sclerosis, Crohn's disease, ulcerative colitis, Sjorgens syndrome, Hashimoto's thyroiditis, Graves Disease, autoimmune hepatitis, and myasthenia gravis.
16. A method to generate an antigen specific anti-inflammatory regulatory T cell, the method comprising:
contacting an antigen presenting cell (APC) with a zwitterionic polysaccharide conjugated to the antigen in vitro in absence of a regulatory T cell to generate an APC presenting the antigen, and thereafter
contacting the APC presenting the antigen with the regulatory T cell to generate an antigen specific regulatory T cell capable of inhibiting a pro-inflammatory response against the antigen,
wherein the zwitterionic polysaccharide is selected from polysaccharide A (PSA) and polysaccharide B (PSB) from B. fragilis and the APC is a dendritic cell,
wherein the antigen is associated with a condition selected from the group consisting of rheumatoid arthritis, myocarditis, scleroderma, type I diabetes, multiple sclerosis, Crohn's disease, ulcerative colitis, Sjorgens syndrome, Hashimoto's thyroiditis, Graves Disease, autoimmune hepatitis, and myasthenia gravis, and
wherein the antigen is a self-antigen.
17. The method of claim 16 , wherein the zwitterionic polysaccharide is conjugated to the antigen by inclusion of the zwitterionic polysaccharide and the antigen on or within a same vesicle.
18. The method of claim 16 , wherein the pro-inflammatory response is a cell mediated inflammatory response.
19. The method of claim 16 , wherein the pro-inflammatory response is a humoral inflammatory response.