The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/8/385/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 3, August 2, 1999 385-398

Original Article

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
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.44-171-982-612144-171-982-6123

ychernaj{at}hgmp.mrc.ac.uk

Galectin-1 (GAL-1), a member of a family of conserved β-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

1used in this paper: CIA, collagen-induced arthritis; CII, collagen type II; GAL-1, galectin-1; mGAL-1, mouse GAL-1; PI, propidium iodide; RA, rheumatoid arthritis; rGAL-1, human recombinant GAL-1; TDG, thiodigalactoside

Gordon Daly and Hanna Dreja contributed equally to this work.

© 1999 The Rockefeller University Press


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