METHODS AND COMPOSITIONS FOR REGULATING LYMPHOCYTE ACTIVITY
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Abstract
The present application is directed to the discovery that hedgehog gene products, and signal transduction pathways involving hedgehog, are involved in maturation of T lymphocytes. The invention provides a method to promote T lymphocyte development using low dose Hedghog, and a method to inhibit T lymphocyte development using high dose Hedgehog. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, agonists, antagonists, or other molecules which regulate patched or smoothened signalling, and their uses as immunomodulatory agents.
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52 Claims
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1-42. -42. (canceled)
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43. A method for promoting thymic T cell maturation in an animal in need thereof, comprising administering to said animal a hedgehog (HH) antagonist in an amount sufficient to promote T cell maturation in the thymus of said animal, whereby said antagonist promotes T cell maturation in the thymus;
- and wherein said HH antagonist is selected from (i) a polypeptide having an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs;
10-18, wherein the polypeptide binds to a patched protein but does not promote hedgehog signaling;
(ii) an antisense construct capable of inhibiting expression of a peptide selected from the group consisting of;
Dhh, Shh, Ihh, Thh, smoothened, and Gli;
or (iii) a small organic molecule, which small organic molecule is a steroidal alkaloid. - View Dependent Claims (44, 45, 46, 47, 48, 49, 50, 51, 52)
- and wherein said HH antagonist is selected from (i) a polypeptide having an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs;
Specification