Treatment of Uveitis by In Situ Administration of Ex Vivo-Activated Polyclonal Regulatory T Cells.

Abstract

CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell therapy is a promising approach for the treatment of autoimmune diseases. To be effective, Treg cells should be in an activated state in the target tissue. This can be achieved by systemic administration of Ag-specific Treg cells, which are difficult to produce in conditions that can be translated to the clinic. In this paper, we propose an alternative approach consisting of in situ injection of preactivated polyclonal Treg cells that would exert bystander suppression in the target tissue. We show that polyclonal Treg cells suppressed uveitis in mice as efficiently as Ag-specific Treg cells but only when preactivated and administered in the vitreous. Uveitis control was correlated with an increase of IL-10 and a decrease of reactive oxygen species produced by immune cell infiltrates in the eye. Thus, our results reveal a new mechanism of Treg cell-mediated suppression and a new Treg cell therapy approach.

• Authors: Sylvie Grégoire, Céline Terrada, Gaelle H Martin, Gwladys Fourcade, Audrey Baeyens, Gilles Marodon, Sylvain Fisson, Fabienne Billiard, Bruno Lucas, Ramin Tadayoni, Francine Béhar-Cohen, Béatrice Levacher, Anne Galy, Phuc LeHoang, David Klatzmann, Bahram Bodaghi, Benoît L Salomon
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 196 Issue 5 Pg. 2109-18 (Mar 01 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 26826251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Topics

• Animals
• Disease Models, Animal
• Female
• Flow Cytometry
• Immunotherapy (methods)
• Lymphocyte Activation (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• T-Lymphocytes, Regulatory (immunology, transplantation)
• Uveitis (immunology)