Method of treating immune pathologies with low dose estrogen
The invention provides a method of ameliorating a Th1-mediated immune pathology in a mammal. The method is practiced by administering a low dose of estrogen to the mammal. Optionally, an immunotherapeutic agent can also be administered to the mammal. Also provided are kits containing a low dose of estrogen and an immunotherapeutic agent.
1. A method of ameliorating multiple sclerosis in a human subject, comprising
administering a dose of estrogen to said human subject sufficient to raise the serum concentration of estrogen in said human to within the range from 30 pg/ml to 1000 pg/ml and
administering a therapeutically effective amount of a T cell receptor peptide comprising a human Vβ2, Vβ5.1, Vβ5.2, Vβ6.1, Vβ6.5, Vβ7, or a Vβ13 T cell receptor peptide CDR2 region, or an analog of a Vβ5.2 T cell receptor peptide comprising the amino acid sequence set forth as SEQ ID NO: 3, to said human subject
thereby ameliorating multiple sclerosis in said human subject.
2. The method of claim 1 , wherein said human subject is female.
3. The method of claim 1 , wherein said human subject is male.
4. The method of claim 1 , wherein said estrogen is selected from the group consisting of 17β-estradiol, estriol and estrone.
5. The method of claim 4 , wherein said estrogen is 17β-estradiol.
6. The method of claim 1 , wherein said dose of estrogen is an amount sufficient to raise the serum concentration of estrogen in said human to within the range from 50 pg/ml to 500 pg/ml.
7. The method of claim 1 , wherein said dose of estrogen is an amount sufficient to raise the serum concentration of estrogen to within the range from 100 pg/ml to 250 pg/ml.
8. The method of claim 1 , wherein said estrogen is administered by a route selected from oral, transdermal, respiratory, subcutaneous and intravenous routes.
9. The method of claim 1 , wherein said amelioration is apparent by magnetic resonance imaging.
10. The method of claim 1 , wherein the T cell receptor peptide comprises a Vβ CDR2 region comprising a Vβ2, Vβ5.1, Vβ5.2, Vβ6.1, Vβ6.5, Vβ7, or a Vβ13 amino acid sequence set forth in Table 2.
11. The method of claim 1 , wherein the T cell receptor peptide comprises a Vβ5.2, Vβ6.5 or Vβ13 CDR2 region.
12. The method of claim 10 , wherein the T cell receptor peptide comprises a Vβ5.2, Vβ6.5 or Vβ13 CDR2 region.
13. The method of claim 10 , wherein the T cell receptor peptide comprises a Vβ5.2 CDR2 region.
14. The method of claim 1 , wherein Vβ CDR2 region consists of a Vβ2 amino acid sequence set forth as one of SEQ ID NOs: 11-14; a Vβ5.1 amino acid sequence set forth as one of SEQ ID NO: 17 or SEQ ID NO:18; a Vβ5.2 amino acid sequence set forth as one of SEQ ID NOs: 2-3 or SEQ ID NO: 19, a Vβ6.1 amino acid sequence set forth as one of SEQ ID NO: 4, SEQ ID NO: 24 or SEQ ID NO: 25, a Vβ6.5 amino acid sequence set forth as one of SEQ ID NO: 5 or SEQ ID NO: 30; a Vβ7 amino acid sequence set forth as one of SEQ ID NOs: 33-55; or a Vβ13 amino acid sequence set forth as one of SEQ ID NO: 6 or SEQ ID NOs: 47-53.
15. A method of ameliorating multiple sclerosis in a human subject, comprising administering a dose of estrogen to said human subject sufficient to raise the serum concentration of estrogen in said human to within the range from 30 pg/ml to 1000 pg/ml and administering a therapeutically effective amount of a T cell receptor peptide comprising a Vβ5.2 CDR2 region, a therapeutically effective amount of a T cell receptor peptide comprising Vβ6.5 CDR2 region, and a therapeutically effective amount of a T cell receptor peptide comprising a Vβ13 CDR2 region, to said human subject thereby ameliorating multiple sclerosis in said human subject.
16. The method of claim 11 , wherein the Vβ5.2 CDR2 region consists of the amino acid sequence set forth as one of SEQ ID NOs: 2-3 or SEQ ID NO: 19; the Vβ6.5 CDR2 region consists of the amino acid sequence set forth as one of SEQ ID NO: 5 or SEQ ID NO: 30; and the Vβ13 CDR2 region consists of the amino acid sequence set forth as one of SEQ ID NO: 6 or SEQ ID NOs: 47-53.
17. The method of claim 11 , wherein the Vβ5.2 CDR2 region consists of one of the amino acid sequence set forth as one of SEQ ID NO: 2 or SEQ ID NO: 3; the Vβ6.5 CDR2 region consists of the amino acid sequence set forth as SEQ ID NO: 5; and the Vβ13 CDR2 region consists of the amino acid sequence set forth as SEQ ID NO: 6.
18. The method of claim 15 , wherein the Vβ5.2 CDR2 region consists of one of the amino acid sequence set forth as one of SEQ ID NO: 2 or SEQ ID NO: 3; the Vβ6.5 CDR2 region consists of the amino acid sequence set forth as SEQ ID NO: 5; and the Vβ13 CDR2 region consists of the amino acid sequence set forth as SEQ ID NO: 6.