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Method of modulating T cell functioning

A cellular and functional technology, applied in the field of regulating TH1 cell function, treating and/or preventing diseases characterized by abnormal, excessive or inappropriate TH1 cell function, and can solve problems such as low tryptophan specificity

Inactive Publication Date: 2008-07-30
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

IDO is less specific for tryptophan than hepatic tryptophan oxidase

Method used

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  • Method of modulating T cell functioning
  • Method of modulating T cell functioning
  • Method of modulating T cell functioning

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Experimental program
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Embodiment 1

[0325] Treatment of confirmed autoimmune neuritis with 3,4-DAA (orally active synthetic TRP metabolite)

[0326] result

[0327] Identification of differentially regulated gene transcripts in APL-treated T cells. Thus, a T cell line was generated from mice bearing a transgenic TCR specific for the myelin basic protein (MBP) peptide Acl-11, and microarray analysis was performed. The allosteric peptide ligand Acl-11[4Y] binds major histocompatibility complex (MHC) class II I-A with higher affinity than native peptide u . Although Acl-11 mainly induces T H 1 response, Acl-11[4Y] starts T H 2 response (Pearson et al. JExp Med. 185:583-99, 1997). Microarray analysis reveals upregulation of indoleamine-2,3-dioxygenase (IDO) transcripts in Acl-11[4Y]-activated T cells after 48 h compared with Acl-11-activated cells increased by more than 70 times (Table 1).

[0328] Table 1: T cell transcripts specifically induced by APL MBP Acl-11[4Y]

[0329]

[0330]

[0331] Trp met...

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Abstract

A method of modulating TH1 cell functioning in a mammal, comprising administering to the mammal an effective amount of one or more IDO-mediated tryptophan metabolites or derivatives thereof; or an antagonist thereof.

Description

field of invention [0001] The present invention generally relates to a method of regulating cell function and reagents therefor. More specifically, the present invention relates to a kind of adopt tryptophan metabolite or derivative thereof, such as the compound of formula (I) to regulate T H 1 Methods of cell function. The method of the present invention is especially suitable for the treatment and / or prophylaxis of T H 1 Disorders characterized by abnormal, excessive or inappropriate cellular function, especially for autoimmune T H 1 function, such as the self-reactive T H 1 answer becomes T H 2 answers. Background technique [0002] In this specification, the details of the bibliography of the publications to which the author refers are listed in alphabetical order at the end of the detailed description section. [0003] "Autoimmune disease" describes a group of disorders that mislead the immune system and attack an organ or organs that are actually supposed to be p...

Claims

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Application Information

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IPC IPC(8): A61K31/195
CPCA61K31/196A61P25/00A61P25/02A61P37/00A61P37/02A61P37/04A61P43/00A61K31/198
Inventor L·斯坦曼M·普拉藤P·P·霍M·L·塞利
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV