What is claimed is:
1. A method of ameliorating a Th1-mediated immune pathology in a mammal, comprising administering a low dose of estrogen to said mammal.
2. The method of claim 1, wherein said Th1-mediated immune pathology is an autoimmune pathology.
3. The method of claim 2, wherein said autoimmune pathology is selected from the group consisting of multiple sclerosis, rheumatoid arthritis and psoriasis.
4. The method of any of claims 1-3, wherein said mammal is female.
5. The method of any of claims 1-3, wherein said mammal is male.
6. The method of any of claims 1-5, wherein said mammal is a human.
7. The method of any of claims 1-6, wherein said estrogen is selected from the group consisting of 17-estradiol, estriol and estrone.
8. The method of claim 7, wherein said estrogen is 17-estradiol.
9. The method of any of claims 1-8, wherein said low dose of estrogen is an amount sufficient to raise the serum concentration of estrogen in said mammal to within the range from 30 pgml to 1000 pgml.
10. The method of any of claims 1-8, wherein said low dose of estrogen is an amount sufficient to raise the serum concentration of estrogen in said mammal to within the range from 50 pgml to 500 pgml.
11. The method of any of claims 1-8, wherein said low dose of estrogen is an amount sufficient to raise the serum concentration of estrogen to within the range from 100 pgml to 250 pgml.
12. The method of any of claims 1-11, wherein said estrogen is administered by a route selected from oral, transdermal, respiratory, subcutaneous and intravenous routes.
13. The method of any of claims 1-12, wherein said amelioration is apparent by magnetic resonance imaging.
14. The method of any of claims 1-13, further comprising administering an immunotherapeutic agent to said mammal.
15. The method of claim 14, wherein said immunotherapeutic agent is an immunomodulatory agent.
16. The method of claim 15, wherein said immunomodulatory agent is a peptide selected from the group consisting of an antigen peptide, an HLA peptide, a T cell receptor peptide and an analog of any of said peptides that induces substantially the same immune response as said peptide.
17. The method of claim 16, wherein said immunomodulatory agent is a T cell receptor peptide or an analog thereof that induces substantially the same immune response as said T cell receptor peptide.
18. The method of claim 17, wherein said T cell receptor peptide comprises an amino acid sequence selected from the group consisting of human V2, V3, V5.1, V5.2, V6.1, V6.5, V7, V13, V14 and V17 amino acid sequences.
19. The method of claim 16, wherein said T cell receptor peptide comprises at least a part of a CDR2 region.
20. The method of claim 15, wherein said immunomodulatory agent is an expressible nucleic acid molecule that encodes a peptide selected from the group consisting of an antigen peptide, an HLA peptide, a T cell receptor peptide and an analog of any of said peptides that induces substantially the same immune response as said peptide.
21. The method of claim 14, wherein said immunotherapeutic agent is an immunoblocking agent.
22. The method of claim 21, wherein said immunoblocking agent specifically binds a molecule selected from the group consisting of a T cell receptor, an antigen and a HLA molecule.
23. The method of claim 22, wherein said immunoblocking agent specifically binds a T cell receptor variable chain selected from the group consisting of human V2, V3, V5.1, V5.2, V6.1, V6.5, V7, V13, V14 and V17.
24. The method of claim 21, wherein said immunoblocking agent is an antibody.
25. The method of claim 21, wherein said immunoblocking agent is attached to a toxic moiety.
26. The method of claim 21, wherein said immunoblocking agent is an altered peptide ligand.
27. The method of claim 15, wherein said immunotherapeutic agent specifically binds a Th1 cytokine.
28. The method of claim 27, wherein said Th1 cytokine is tumor necrosis factor alpha.
29. The method of claim 15, wherein said immunotherapeutic agent is a purine analog.
30. The method of claim 15, wherein said immunotherapeutic agent is glatiramer acetate.
31. The method of claim 15, wherein said immunotherapeutic agent is a cytokine.
32. The method of claim 31, wherein said cytokine is selected from the group consisting of IFN-1a and IFN-1b.
33. A kit, comprising a low dose of estrogen and an immunotherapeutic agent, wherein administration of said low dose of estrogen and said immunotherapeutic agent ameliorates a Th1-mediated immune pathology in a mammal.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A motor-cycle tire (1) comprising a ground contacting tread (2) reinforced between its edges (3,4) by a breaker assembly and having in its normally inflated fitted condition a camber value CL of between 0.5 and 0.7, a reinforcing carcass ply (14) extending radially inside the breaker assembly and between two bead regions (10,11) and wrapped in each bead region around an annular bead core (12,13) from the axial inside to the outside to form carcass ply turn-ups (15,16) and between the tread edges (3,4) and bead regions (10,11), tire sidewalls (8,9) wherein the breaker assembly comprises two breaker plies (5,7) comprising reinforcing cords oppositely inclined with respect to the circumferential direction of the tire characterised in that the tread comprises two different rubber compounds, a first rubber compound extending in a continuous first layer between the tread edges (3,4) and a second rubber compound disposed in a second layer radially outwardly of the layer of the first rubber compound to form the tread running surface in the central portion of the tread, centred on the tire axial centreline, having a width (S) of between 30% and 50% of the tread width (TW), the widths being measured along the arc of the tread surface, and on an interfacial fabric layer disposed at the boundary between the first and second rubber layers, the cords of the fabric layer are laid parallel to each other and disposed at an angle of 18-30 to the tread circumferential direction and radial thickness of the second layer of rubber is between 50% and 80% of the total radial thickness of the tread.
2. A tire according to claim 1, characterised in that the interfacial fabric layer comprises nylon cords.
3. A tire according to any of claims 1 or 2, characterised in that the radial thickness (t) of the portion of first rubber layer radially inward of the second layer is not less than 2 mm.
4. A tire according to any of claims 1 to 3, characterised in that the hardness of the rubber of the first rubber layer (RL1) at 100 C. lies in range 40-49 Shore A.
5. A tire according to any of claims 1 to 4, characterised in that the first rubber layer (RL1) has a tensile modulus at 300% extension at 100 C. of less than 5.0 MPa.
6. A tire according to any of claims 1 to 5, characterised in that the rubber of the second rubber layer (RL2) has a hardness at 100 C. of not less than 500 Shore A.
7. A tire according to any of claims 1 to 16, characterised in that the rubber of the second rubber layer (RL2) has a tensile modulus at 300% extension at 100 C. of not less than 5.0 MPa.