Manipulation of cytokine levels using cd83 gene products
First Claim
Patent Images
1. A method of modulating cytokine production in a mammal by modulating the activity or expression of a CD83 polypeptide.
2 Assignments
0 Petitions
Accused Products
Abstract
The invention provides methods for modulating cytokine levels, GM-CSF levels and the immune system using CD83 nucleic acids, CD83 polypeptides, anti-CD83 antibodies and factors that influence CD83 activity or expression. The invention also provides mice having a mutant CD83 gene and mice having a transgenic CD83 gene, which are useful for defining the role of CD83 in the immune system and for identifying compounds that can modulate CD83 and the immune system.
9 Citations
62 Claims
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1. A method of modulating cytokine production in a mammal by modulating the activity or expression of a CD83 polypeptide.
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2. A method of modulating cytokine production in a mammal by administering to the mammal an antibody that can modulate the activity or expression of a CD83 polypeptide.
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3. A method of modulating cytokine production by a T cell by modulating the activity or expression of a CD83 polypeptide in the T cell.
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4. A method of modulating cytokine production by a T cell by contacting the T cell with an antibody that can modulate the activity or expression of a CD83 polypeptide.
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5. A method of modulating a CD4+ T cell by modulating the activity or expression of a CD83 polypeptide in the T cell.
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6. A method of modulating a CD4+ T cell by contacting the T cell with an antibody that can modulate the activity or expression of a CD83 polypeptide.
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7. A method of modulating granulocyte macrophage colony stimulating factor production in a mammal by modulating the activity or expression of CD83 polypeptides.
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8. A method of modulating granulocyte macrophage colony stimulating factor production in a mammal by administering to the mammal an antibody that can modulate the activity or expression of CD83 polypeptides.
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9. A method of modulating granulocyte macrophage colony stimulating factor production by a T cell by modulating the activity or expression of a CD83 polypeptide in the T cell.
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10. A method of modulating granulocyte macrophage colony stimulating factor production by a T cell by contacting the T cell with an antibody that can modulate the activity or expression of a CD83 polypeptide.
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11. A method of tumor necrosis factor production in a mammal by modulating the activity or expression of CD83 polypeptides.
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12. A method of modulating tumor necrosis factor production in a mammal by administering to the mammal an antibody that can modulate the activity or to expression of CD83 polypeptides.
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13. A method of inhibiting proliferation of a human peripheral blood mononuclear cell by modulating the activity or expression of CD83 polypeptides.
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14. A method of inhibiting proliferation of a human peripheral blood mononuclear cell in a mammal by administering to the mammal an antibody that can modulate the activity or expression of CD83 polypeptides.
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15. An antibody that can bind to a CD83 polypeptide comprising SEQ ID NO:
- 4, SEQ ID NO;
8 or SEQ ID NO;
9, wherein activated CD4+ T-cells produce lower levels of interleukin-4 when said T-cells are contacted with the antibody.
- 4, SEQ ID NO;
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16. An antibody that can bind to a CD83 polypeptide comprising SEQ ID NO:
- 4, SEQ ID NO;
8 or SEQ ID NO;
9, wherein CD4+ T-cells proliferation is decreased when said T-cells are contacted with the antibody.
- 4, SEQ ID NO;
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17. An antibody comprising SEQ ID NO:
- 11, SEQ ID NO;
13, SEQ ID NO;
15, SEQ ID NO;
17, SEQ ID NO;
19, SEQ ID NO;
21, SEQ ID NO;
23, SEQ ID NO;
24, SEQ ID NO;
25, SEQ ID NO;
26, SEQ ID NO;
27, SEQ ID NO;
28, SEQ ID NO;
29, SEQ ID NO;
30, SEQ ID NO;
31, SEQ ID NO;
32, SEQ ID NO;
33, SEQ ID NO;
34, SEQ ID NO;
35, SEQ ID NO;
36, SEQ ID NO;
37, SEQ ID NO;
38, SEQ ID NO;
39, SEQ ID NO;
40, SEQ ID NO;
41, SEQ ID NO;
42, SEQ ID NO;
43, SEQ ID NO;
44, SEQ ID NO;
45, SEQ ID NO;
46, SEQ ID NO;
47, SEQ ID NO;
48, SEQ ID NO;
52, SEQ ID NO;
53, SEQ ID NO;
54, SEQ ID NO;
55, SEQ ID NO;
56, SEQ ID NO;
57, SEQ ID NO;
58, SEQ ID NO;
60, SEQ ID NO;
62 or SEQ ID NO;
64.
- 11, SEQ ID NO;
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18. A nucleic acid encoding an antibody comprising SEQ ID NO:
- 11, SEQ ID NO;
13, SEQ ID NO;
15, SEQ ID NO;
17, SEQ ID NO;
19, SEQ ID NO;
21, SEQ ID NO;
23, SEQ ID NO;
24, SEQ ID NO;
25, SEQ ID NO;
26, SEQ ID NO;
27, SEQ ID NO;
28, SEQ ID NO;
29, SEQ ID NO;
30, SEQ ID NO;
31, SEQ ID NO;
32, SEQ ID NO;
33, SEQ ID NO;
34, SEQ ID NO;
35, SEQ ID NO;
36, SEQ ID NO;
37, SEQ ID NO;
38, SEQ ID NO;
39, SEQ ID NO;
40, SEQ ID NO;
41, SEQ ID NO;
42, SEQ ID NO;
43, SEQ ID NO;
44, SEQ ID NO;
45, SEQ ID NO;
46, SEQ ID NO;
47, SEQ ID NO;
48, SEQ ID NO;
52, SEQ ID NO;
53, SEQ ID NO;
54, SEQ ID NO;
55, SEQ ID NO;
56, SEQ ID NO;
57, SEQ ID NO;
58, SEQ ID NO;
60, SEQ ID NO;
62 or SEQ ID NO;
64. - View Dependent Claims (19)
- 11, SEQ ID NO;
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20. A method for decreasing the activity of a CD83 gene product, comprising contacting the CD83 gene product with an antibody that comprises SEQ ID NO:
- 11, SEQ ID NO;
13, SEQ ID NO;
15, SEQ ID NO;
17, SEQ ID NO;
19, SEQ ID NO;
21, SEQ ID NO;
23, SEQ ID NO;
24, SEQ ID NO;
25, SEQ ID NO;
26, SEQ ID NO;
27, SEQ ID NO;
28, SEQ ID NO;
29, SEQ ID NO;
30, SEQ ID NO;
31, SEQ ID NO;
32, SEQ ID NO;
33, SEQ ID NO;
34, SEQ ID NO;
35, SEQ ID NO;
36, SEQ ID NO;
37, SEQ ID NO;
38, SEQ ID NO;
39, SEQ ID NO;
40, SEQ ID NO;
41, SEQ ID NO;
42, SEQ ID NO;
43, SEQ ID NO;
44, SEQ ID NO;
45, SEQ ID NO;
46, SEQ ID NO;
47, SEQ ID NO;
48, SEQ ID NO;
52, SEQ ID NO;
53, SEQ ID NO;
54, SEQ ID NO;
55, SEQ ID NO;
56, SEQ ID NO;
57, SEQ ID NO;
58, SEQ ID NO;
60, SEQ ID NO;
62 or SEQ ID NO;
64.
- 11, SEQ ID NO;
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21. A method for decreasing the activity of a CD83 gene product in a mammal, comprising administering to the mammal an antibody that comprises SEQ ID NO:
- 11, SEQ ID NO;
13, SEQ ID NO;
15, SEQ ID NO;
17, SEQ ID NO;
19, SEQ ID NO;
21, SEQ ID NO;
23, SEQ ID NO;
24, SEQ ID NO;
25, SEQ ID NO;
26, SEQ ID NO;
27, SEQ ID NO;
28, SEQ ID NO;
29, SEQ ID NO;
30, SEQ ID NO;
31, SEQ ID NO;
32, SEQ ID NO;
33, SEQ ID NO;
34, SEQ ID NO;
35, SEQ ID NO;
36, SEQ ID NO;
37, SEQ ID NO;
38, SEQ ID NO;
39, SEQ ID NO;
40, SEQ ID NO;
41, SEQ ID NO;
42, SEQ ID NO;
43, SEQ ID NO;
44, SEQ ID NO;
45, SEQ ID NO;
46, SEQ ID NO;
47, SEQ ID NO;
48, SEQ ID NO;
52, SEQ ID NO;
53, SEQ ID NO;
54, SEQ ID NO;
55, SEQ ID NO;
56, SEQ ID NO;
57, SEQ ID NO;
58, SEQ ID NO;
60, SEQ ID NO;
62 or SEQ ID NO;
64.
- 11, SEQ ID NO;
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22. A method for decreasing the translation of a CD83 gene product in a mammalian cell, comprising contacting the mammalian cell with a nucleic acid complementary to a CD83 nucleic acid comprising SEQ ID NO:
- 1, SEQ ID NO;
3, SEQ ID NO;
5, or SEQ ID NO;
10.
- 1, SEQ ID NO;
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23. A method for decreasing the translation of a CD83 gene product in a mammal, comprising administering to the mammal a nucleic acid complementary to a CD83 nucleic acid comprising SEQ ID NO:
- 1, SEQ ID NO;
3, SEQ ID NO;
5, or SEQ ID NO;
10.
- 1, SEQ ID NO;
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24. A method for decreasing proliferation of CD4+ T-cells in a mammal comprising administering to the mammal an antibody that can bind to a CD83 gene product, wherein the CD83 gene product comprises SEQ ID NO:
- 2 or SEQ ID NO;
9. - View Dependent Claims (25)
- 2 or SEQ ID NO;
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26. A method for decreasing interleukin-2 levels and increasing interleukin-4 levels in a mammal comprising administering to the mammal an antibody that can bind to a CD83 gene product, wherein the CD83 gene product comprises SEQ ID NO:
- 2 or SEQ ID NO;
9. - View Dependent Claims (27, 29, 30, 31, 32, 33, 34)
- 2 or SEQ ID NO;
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28. A method for decreasing interleukin-2 levels and increasing interleukin-4 levels in a mammal comprising administering to the mammal a nucleic acid complementary to a CD83 nucleic acid comprising SEQ ID NO:
- 1, SEQ ID NO;
3, SEQ ID NO;
5, or SEQ ID NO;
10.
- 1, SEQ ID NO;
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35. A method for increasing interleukin-10 levels in a mammal comprising administering to the mammal an antibody that can bind to a CD83 gene product, wherein the CD83 gene product comprises SEQ ID NO:
- 2 or SEQ ID NO;
9. - View Dependent Claims (36, 38, 39)
- 2 or SEQ ID NO;
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37. A method for increasing interleukin-10 levels in a mammal comprising administering to the mammal a nucleic acid complementary to a CD83 nucleic acid comprising SEQ ID NO:
- 1, SEQ ID NO;
3, SEQ ID NO;
5, or SEQ ID NO;
10.
- 1, SEQ ID NO;
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40. A method for increasing interleukin-2 levels in a mammal comprising administering to the mammal a functional CD83 polypeptide that comprises SEQ ID NO:
- 9.
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41. A method for increasing interleukin-2 levels in a mammal comprising:
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(a) transforming a T cell from the mammal with a nucleic acid encoding a functional CD83 polypeptide operably linked to a promoter functional in a mammalian cell, to generate a transformed T cell;
(b) administering the transformed T cell to the mammal to provide increased levels of interleukin-2. - View Dependent Claims (42, 43, 44, 45, 46, 47, 48, 49, 50, 51)
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52. A method for increasing granulocyte macrophage colony stimulating factor levels in a mammal comprising administering to the mammal an antibody that can bind to a CD83 gene product, wherein the CD83 gene product comprises SEQ ID NO:
- 2 or SEQ ID NO;
9. - View Dependent Claims (53)
- 2 or SEQ ID NO;
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54. A method for increasing granulocyte macrophage colony stimulating factor levels in a mammal comprising administering to the mammal a nucleic acid complementary to a CD83 nucleic acid comprising SEQ ID NO:
- 1, SEQ ID NO;
3, SEQ ID NO;
5, or SEQ ID NO;
10.
- 1, SEQ ID NO;
- 55. A method for increasing tumor necrosis factor levels at a selected site in a mammal comprising administering to the site a functional CD83 polypeptide.
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56. A method for increasing tumor necrosis factor levels in a selected mammalian cell comprising transforming the cell with a nucleic acid encoding a functional CD83 polypeptide.
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58. A method of identifying a compound that can modulate CD4+T cell activation comprising administering a test compound to a mutant mouse and observing whether CD4+ T cells become activated, wherein the somatic and germ cells of the mutant mouse comprise a mutant CD83 gene encoding a polypeptide comprising SEQ ID NO:
- 4 or SEQ ID NO;
8.
- 4 or SEQ ID NO;
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59. A mutant CD83 gene encoding a polypeptide comprising SEQ ID NO:
- 4 or SEQ ID NO;
8.
- 4 or SEQ ID NO;
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60. The mutant CD83 gene of claim 63 comprising nucleotide sequence SEQ ID NO:
- 3.
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61. A mutant mouse whose somatic and germ cells comprise a mutant CD83 gene encoding a polypeptide comprising SEQ ID NO:
- 4 or SEQ ID NO;
8, wherein expression of said mutant CD83 gene reduces CD4+T cell activation. - View Dependent Claims (62)
- 4 or SEQ ID NO;
Specification