The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rabinovich, G. A.
Right arrow Articles by Chernajovsky, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rabinovich, G. A.
Right arrow Articles by Chernajovsky, Y.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
J. Exp. Med., Volume 190, Number 3, August 2, 1999 385-398
Copyright © 1999 by The Rockefeller University Press.

Recombinant Galectin-1 and Its Genetic Delivery Suppress Collagen-induced Arthritis via T Cell Apoptosis

Gabriel A. Rabinovicha, Gordon Dalyb, Hanna Drejab, Hitakshi Tailorb, Clelia M. Rieraa, Jun Hirabayashic, and Yuti Chernajovskyb
a From Immunology, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Córdoba 5000, CC61 Córdoba, Argentina
b Molecular Biology Laboratory, The Kennedy Institute of Rheumatology, Hammersmith W6 8LH, London, United Kingdom
c Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan

Correspondence to: Yuti Chernajovsky, Bone and Joint Unit, St. Bartholomew's and Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom., ychernaj{at}hgmp.mrc.ac.uk (E-mail), 44-171-982-6123 (phone), 44-171-982-6121 (fax)

Galectin-1 (GAL-1), a member of a family of conserved ß-galactoside–binding proteins, has been shown to induce in vitro apoptosis of activated T cells and immature thymocytes. We assessed the therapeutic effects and mechanisms of action of delivery of GAL-1 in a collagen-induced arthritis model. A single injection of syngeneic DBA/1 fibroblasts engineered to secrete GAL-1 at the day of disease onset was able to abrogate clinical and histopathological manifestations of arthritis. This effect was reproduced by daily administration of recombinant GAL-1. GAL-1 treatment resulted in reduction in anticollagen immunoglobulin (Ig)G levels. The cytokine profile in draining lymph node cells and the anticollagen IgG isotypes in mice sera at the end of the treatment clearly showed inhibition of the proinflammatory response and skewing towards a type 2–polarized immune reaction. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. Moreover, GAL-1–expressing fibroblasts and recombinant GAL-1 revealed a specific dose-dependent inhibitory effect in vitro in antigen-dependent interleukin 2 production to an Aq-restricted, collagen type 2–specific T cell hybridoma clone. Thus, a correlation between the apoptotic properties of GAL-1 in vitro and its immunomodulatory properties in vivo supports its therapeutic potential in the treatment of T helper cell type 1–mediated autoimmune disorders.

Key Words: galectin-1, gene therapy, apoptosis, collagen-induced arthritis, T cells


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS