Methods and compositions for modulating the activity of the interleukin-35 receptor complex

a technology of interleukin-35 receptor and activity regulation, which is applied in the direction of drug compositions, immunoglobulins, peptides against animals/humans, etc., can solve the problems of undesirable effector t cells, relapse of disease, and numerous harmful side effects

Inactive Publication Date: 2012-12-27
ST JUDE CHILDRENS RES HOSPITAL INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in other situations, such effector T cells are undesirable, e.g., in a graft recipient.
General immunosuppressants must be administered fr

Method used

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  • Methods and compositions for modulating the activity of the interleukin-35 receptor complex
  • Methods and compositions for modulating the activity of the interleukin-35 receptor complex
  • Methods and compositions for modulating the activity of the interleukin-35 receptor complex

Examples

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example 1

IL-35 Signaling and Suppression Mediated by IL-35 Require the Expression of the IL-35R

Materials and Methods:

[0176]Mice. C57BL / 6 (wild type), CD4.cre, and IL12Rβ2− / − mice were purchased from the Jackson Laboratory. Gp130 floxed knockin mice were provided by Rodger McEver at Oklahoma Medical Research Foundation. gp130 fl×CD4.cre×IL12Rb2− / − were obtained by breeding the three mouse strains listed. All animal experiments were performed in American Association for the Accreditation of Laboratory Animal Care-accredited, specific-pathogen-free facilities in the St. Jude Animal Resource Center following national, state and institutional guidelines. Animal protocols were approved by the St Jude Animal Care and Use Committee.

[0177]Tconv Cell Purification. Teff(CD4+CD25−CD45RBhi) from the spleens and lymph nodes of C57BL / 6 or knockout age-matched gp130.fl×CD4.cre×IL12Rb2− / − mice were positively sorted by FACS. After red blood cell lysis, cells were stained with antibodies against CD4, CD25 and...

example 2

IL-35 Signals Primarily Through Two Different STAT Proteins, STAT1 and STAT4

Materials and Methods:

[0182]Mice. Spleens and lymph nodes from Il12rb1− / − mice were provided by D. Fairweather and J. A. Frisancho (Johns Hopkins University), CD4cre×gp130fl / fl mice were provided by M. Karin and S. Grivennikov (University of California at San Diego), IL27ra− / − mice were provided by C. Hunter and J. Stumhofer (University of Pennsylvania), Stat1− / − mice were provided by A. Satoskar and P. Reville (Ohio State University), and Stat3− / − mice were provided by C. Drake and H.R. Yen (Johns Hopkins University). IL12rb2− / −, Stat4− / −, Rag1− / −, C57BL / 6, B6.PL and Balb / c mice were purchased from the Jackson Laboratory. All animal experiments were performed in American Association for the Accreditation of Laboratory Animal Care-accredited, specific-pathogen-free facilities in the St. Jude Animal Resource Center following national, state and institutional guidelines. Animal protocols were approved by the S...

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Abstract

The receptor for Interleukin 35 (IL-35) is provided. The Interleukin 35 Receptor (IL-35R) comprises a heterodimeric complex of the Interluekin12Rβ2 receptor and the gp130 receptor. Various compositions comprising the IL-35R complex, along with polynucleotides encoding the same and kits and methods for the detection of the same the same are provided. Methods of modulating the activity of IL-35R or modulating effector T cell functions are also provided. Such methods employ various IL-35R antagonists and agonists that modulate the activity of the IL-35R complex and, in some embodiments, modulate effector T cell function. Further provided are methods for screening for IL-35R binding agents and for IL-35R modulating agents. Various methods of treatment are further provided.

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods for regulating T cell function in a subject, particularly effector T cell activity.REFERENCE TO A SEQUENCE LISTING SUBMITTED AS A TEXT FILE VIA EFS-WEB[0002]The official copy of the sequence listing is submitted concurrently with the specification as a text file via EFS-Web, in compliance with the American Standard Code for Information Interchange (ASCII), with a file name of 397057SEQLIST.txt, a creation date of Nov. 16, 2010, and a size of 61 KB. The sequence listing filed via EFS-Web is part of the specification and is hereby incorporated in its entirety by reference herein.BACKGROUND OF THE INVENTION[0003]The immune system provides the human body with a means to recognize and defend itself against microorganisms, viruses, and substances recognized as foreign and potentially harmful. Classical immune responses are initiated when antigen-presenting cells present an antigen to CD4+ T helper (Th) lymphocytes result...

Claims

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Application Information

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IPC IPC(8): A61K38/17C12Q1/68G01N33/53C12N5/10A61P29/00A61P35/00C07K14/715C07K16/18C07H21/04A01K67/027A61K39/00G01N33/566
CPCA01K2217/05A01K2267/0387A61K2039/505C07K14/7155C12Q2600/158C07K2317/76C12Q1/6883C12Q1/6886C07K16/244A61P29/00A61P35/00C07K16/2866G01N33/505
Inventor VIGNALI, DARIO AACOLLISON, LAUREN W.
Owner ST JUDE CHILDRENS RES HOSPITAL INC
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