HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print August 18, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1205749v1 80/6/1233    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sancho, D. Articles by Sánchez-Madrid, F. Search for Related Content PubMed PubMed Citation Articles by Sancho, D. Articles by Sánchez-Madrid, F. Related Collections Related Article

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1205749

Received for publication December 21, 2005.
Revised April 10, 2006.
Accepted for publication May 11, 2006.

Article

Pivotal Advance: CD69 targeting differentially affects the course of collagen-induced arthritis

David Sancho ^*, Manuel Gómez ^*, Gloria Martinez del Hoyo ^*, Amalia Lamana ^*, Enric Esplugues , Pilar Lauzurica , Carlos Martinez-A , and Francisco Sánchez-Madrid ^*@

*Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain; Departamento de Fisiología, Universidad de Barcelona, Barcelona, Spain; and Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain

^@ To whom correspondence should be addressed. E-mail: fsanchez.hlpr{at}salud.madrid.org.

	Abstract

CD69 expression is induced following activation of leukocytes at inflammatory sites and plays a negative regulatory role in the development of collagen-induced arthritis (CIA). To evaluate potential strategies of CD69 targeting in chronic inflammatory diseases, two different anti-CD69 mAbs were generated and their effects on CIA were studied. Administration of the IgG1 anti-CD69 mAb 2.2 to DBA/1 mice with CIA led to an exacerbation of the disease, correlated with down-modulation of CD69 from the cell surface, and reproduced the phenotype of the CD69(-/-) mouse in wild-type animals. In contrast, treatment with the IgG2a anti-CD69 mAb 2.3 was effective in ameliorating CIA when administered in the early or intermediate phases of the disease, causing a decreased production of proinflammatory cytokines in inflammatory foci. Monoclonal antibody 2.3 induces partial depletion of CD69+ cells in vivo. Moreover, adoptive transfer of type-II collagen (CII)-sensitized cells treated with mAb 2.3 to deplete CD69+ cells did not result in arthritis. The attenuation of inflammation correlates with reduced lymphocyte proliferative response in response to CII and with a reduction in the frequency of CII-specific T cells producing IFN-. We thus conclude that CD69 targeting by mAbs can either enhance or dampen the immune response.

Key Words: antibodies • autoimmunity • T cells • cytokines • chemokines

Related Article

Interview with Dr. Francisco Sánchez-Madrid regarding Pivotal Advance: CD69 targeting differentially affects the course of collagen-induced arthritis

Helene F. Rosenberg
J. Leukoc. Biol. 2006 80: 1231-1232. [Full Text] [PDF]

This article has been cited by other articles:

				M. Gomez, S. M. Sanz-Gonzalez, Y. N. A. Nabah, A. Lamana, F. Sanchez-Madrid, and V. Andres Atherosclerosis development in apolipoprotein E-null mice deficient for CD69 Cardiovasc Res, September 4, 2008; (2008) cvn227v2. [Abstract] [Full Text] [PDF]