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Mol. Hum. Reprod. Advance Access published online on September 20, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam067
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Expression of Costimulatory Molecules, Chemokine Receptors and Proinflammatory Cytokines in Dendritic Cells from Normal and Chronically Inflamed Rat Testis

Claudia Rival1, Vanesa A. Guazzone1, Werner von Wulffen2, Holger Hackstein3, Eva Schneider4, Livia Lustig1, Andreas Meinhardt4,# and Monika Fijak4

1Center for Research in Reproduction, School of Medicine, University of Buenos Aires, Argentina 2Department of Pulmonary and Critical Care Medicine, University of Giessen Lung Center 3Institute for Clinical Immunology and Transfusion Medicine 4Department of Anatomy and Cell Biology, Justus-Liebig-University of Giessen, Germany

# Corresponding author: Dr. Andreas Meinhardt, PhD, Department of Anatomy and Cell Biology, Justus-Liebig-University of Giessen, Aulweg 123 D-35385 Giessen, Germany Phone: +49-641-9947024 Fax: +49-641-9947029 Email: andreas.meinhardt{at}anatomie.med.uni-giessen.de

The presentation of self antigens by dendritic cells (DC) plays an important role in the initiation and maintenance of autoimmunity. In a model of experimental autoimmune orchitis (EAO) we have previously characterized dominant testicular autoantigens and shown an increase in DC numbers during the course of disease. In this study, we have developed a protocol for the isolation of a highly pure population of DC (~97%) from the testis of EAO and control rats to analyze the expression of MHC class II and costimulatory molecules (CD80, CD86), chemokine receptors (CCR2, CCR7) and cytokines (IL-10, IL-12p70, TNF-{alpha}). By flow cytometry, we observed similar percentage and intensity levels of MHC class II, CD80 and CD86 expression in testicular DC in all groups. Moreover, by real time RT-PCR we have detected significantly higher CCR7 mRNA level in isolated testicular DC from rats with EAO compared to controls, while the expression of CCR2 was decreased in orchitis. Transcripts of IL-12p40 were observed in DC from all groups, whereas the expression of IL-10 and the rate limiting IL-12 subunit p35 were detectable exclusively in testicular DC from the inflamed testes. In co-culture experiments testicular DC isolated from EAO animals significantly enhanced naïve T cell proliferation compared to control DC. Taken together these results suggest that testicular DC in control testis are not mature and functionally tolerogenic, whereas in EAO testis IL-12 expression and stimulation of T cell proliferation points to a mature immunogenic state prior imminent migration to the lymph nodes to amplify immune responses against testicular antigens.

Key Words: experimental autoimmune orchitis (EAO)/dendritic cells/testicular inflammation/costimulatory molecules/chemokine receptors/cytokines/testis

Submitted on August 27, 2007; accepted on September 7, 2007.


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[Abstract] [Full Text] [PDF]


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