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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

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Peripheral tolerance induced by apoptotic cells and PD-1+ CD8 T cells

Hirotaka Kazama1*, Tomonori Iyoda1, Satoko Yokoyama1, Kayo Inaba1, Thomas A Ferguson2 and Shin Yonehara1

  • * Corresponding author: Hirotaka Kazama

Author Affiliations

1 Department of Biostudies, Kyoto University Graduate School, Kyoto 606-8501 Japan

2 Department of Ophthalmology and Visual Science, Washington University School of Medicine, MO 63110 USA

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Arthritis Research & Therapy 2012, 14(Suppl 1):P34  doi:10.1186/ar3635

The electronic version of this article is the complete one and can be found online at:

Published:9 February 2012

© 2012 Kazama et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Poster presentation

Self tolerization in peripheral is critical to prevent autoimmune diseases including arthritis and here we focus on the role of PD-1 in tolerance induction against the antigen associated with apoptotic cellsdelivered intravenously (i.v.). We accessed delayed type hypersensitivity (DTH) reaction against hapten (TNP) as antigen specific immune response, in which the injection of TNP-apoptotic cells i.v. suppressed DTH in wild type mice but we found not in PD-1 KO mice (Figure 1). Adaptive transfer of CD8 T cells into PD-1 KO mouse from wild type mice tolerated with TNP-apoptotic cells suppresses DTH. This result shows PD-1 functions on CD8 T cells for immune suppression. Additionally we neutralized the PD-1 with antibody to determine the phase when PD-1 functions for immune tolerance by apoptotic cells, and identified PD-1 functions particularly at the initial phase of antigen specific immune response. We are further studying the mechanism of suppressive role of PD-1+ CD8 T cells that should be activated with apoptotic cells.

thumbnailFigure 1. PD-1 is essential for tolerance induced by apoptotic cells. TNP-apoptotic cells were injected intravenously into PD-1 hetero- or homo- deficient mice. The mice were immunized with TNP (Filled bar) or preconditioned with apoptotic cells before immunization with TNP (open bar).


We were kindly provided the neutralizing antibodies to PD-1 and PD-L2 by Dr. Hideo Yagita (Juntendo University) and hybridoma to PD-L1 from Dr. Miyuki Azuma (Tokyo Medical and Dental University).