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 either:
a) a T 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; or
b) 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.
2 . The method of claim 1 , wherein the polysaccharide is PSA.
3 . The method of claim 1 , wherein the T cell is a regulatory T cell.
4 . The method of claim 1 , further comprising for b) contacting the antigen presenting cell, after said antigen presenting cell contacting with the zwitterionic polysaccharide conjugated to the antigen, with a regulatory T cell.
5 . The method of claim 1 , wherein for b) contacting an antigen presenting cell with a zwitterionic polysaccharide conjugated to the antigen is performed in presence of the regulatory T cell.
6 . 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.
7 . The method of claim 6 , wherein the vesicle is an OMV.
8 . The method of claim 1 , wherein the zwitterionic polysaccharide is conjugated to the antigen by physical connect.
9 . The method of claim 1 , wherein the zwitterionic polysaccharide is conjugated to the antigen by direct or indirect covalent linkage.
10 . The method claim 1 , wherein the pro-inflammatory response is a cell mediated inflammatory response.
11 . The method of claim 1 , wherein the pro-inflammatory response is a humoral inflammatory response.
12 . The method of claim 1 , wherein the contacting is performed in vitro.
13 . The method of claim 1 , wherein the T cells are obtained from an individual patient.
14 . The method of claim 13 , wherein the generated antigen specific anti-inflammatory regulatory T cells are injected back into said individual.
15 . The method of claim 1 , wherein the contacting is performed in vivo.
16 . The method of claim 15 , wherein the contacting is performed by topical or systemic administration of the zwitterionic polysaccharide conjugated to the antigen to allow generation of the antigen specific T reg in the gut of an individual.
17 . The method of claim 1 , 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.
18 . A method of inhibiting antigen specific inflammation in an individual, the method comprising treating the individual with a zwitterionic polysaccharide conjugated to a specific antigen for a time and under conditions to induce an antigen specific anti-inflammatory regulatory T cell in the individual.
19 . The method of claim 18 , wherein the polysaccharide is PSA.
20 . The method of claim 18 , wherein the zwitterionic polysaccharide is conjugated to the antigen by inclusion of the zwitterionic polysaccharide and the antigen on or within a same vesicle.
21 . The method of claim 18 , wherein the zwitterionic polysaccharide is conjugated to the antigen by physical connect.
22 . The method of claim 18 , wherein the zwitterionic polysaccharide is conjugated to the antigen by direct or indirect covalent linkage.
23 . The method of claim 18 , 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.
24 . A method to generate an antigen specific anti-inflammatory regulatory T cell, the method comprising contacting either:
a) a T cell with a zwitterionic polysaccharide 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; or
b) an antigen presenting cell with a zwitterionic polysaccharide 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.
25 . The method of claim 24 , wherein the polysaccharide is PSA.
26 . The method of claim 25 , wherein the zwitterionic polysaccharide is within or on the cell surface of a vesicle.
27 . The method of claim 26 , wherein the vesicle is an OMV.
28 . The method of claim 24 , wherein the zwitterionic polysaccharide is conjugated to an antigen.
29 . The method of claim 24 , wherein the contacting is performed in vitro.
30 . The method of claim 24 , wherein the generated an antigen specific regulatory T cells are injected into a patient.