Integration of the Innate and Adaptive Immunity by CD137-CD137L Bidirectional Signals: Implications in Allograft Rejection

Sang June Park; Jong Soo Lee; Byungsuk Kwon; Hong Rae Cho

doi:10.4285/jkstn.2014.28.3.113

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Park, Lee, Kwon, and Cho: Integration of the Innate and Adaptive Immunity by CD137-CD137L Bidirectional Signals: Implications in Allograft Rejection

Review Article

J Korean Soc Transplant 2014;28(3):113-120.

Published online: 10 September 2014

DOI: https://doi.org/10.4285/jkstn.2014.28.3.113

Integration of the Innate and Adaptive Immunity by CD137-CD137L Bidirectional Signals: Implications in Allograft Rejection

Sang June Park^1,³, Jong Soo Lee^2,³, Byungsuk Kwon^3,⁴, Hong Rae Cho^1,³

¹Departments of Surgery, University of Ulsan, Ulsan, Korea

²Departments of Surgery, Internal Medicine, University of Ulsan, Ulsan, Korea

³Departments of Surgery, Biomedical Research Center, University of Ulsan, Ulsan, Korea

⁴Departments of Surgery, School of Biological Sciences, University of Ulsan, Ulsan, Korea

Corresponding authors Byungsuk Kwon School of Biological Sciences, University of Ulsan, 93 Daehak-ro, Nam-gu, Ulsan 680-749, Korea Tel: 82-52-259-2860, Fax: 82-52-259-2740 E-mail: bkwon@mail.ulsan.ac.kr Hong Rae Cho Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunwhando-ro, Dong-gu, Ulsan 682-714, Korea Tel: 82-52-250-7100, Fax: 82-52-250-8071 E-mail: hrcho@uuh.ulsan.kr

Received 30 August 20143 September 2014 Accepted 3 September 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Two-signal models are useful in explaining various types of immune responses. In particular, secondary, so-called costimulatory, signals are critically required for the process of T-cell activation, survival, differentiation, and memory formation. Early studies in rodent models showed that targeting T-cell costimulatory pathways elicits immunological tolerance, providing a basis for development of costimulatory therapeutics in allograft rejection. However, as the classic definition of T-cell costimulation continues to evolve, simple blockade of costimulatory pathways has limitations in prevention of allograft rejection. Furthermore, functions of costimulatory molecules are much more diverse than initially anticipated and beyond T cells. In this mini-review, we will discuss CD137-CD137L bidirectional signals as examples showing that two-signals can be applicable to multiple phases of immune responses.

Keywords: Costimulation, CD137, CD137L, Immune response

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Fig. 1.

A schematic diagram showing two representative in vivo functions of CD137-CD137L bidirectional signaling. (A) CD137-CD137L interactions occur between NK cells and tubular epithelial cells during ischemia-reperfusion kidney injury. TLR2 and CD137L signaling in tubular epithelial cells induces the production of chemokines required for immune cell recruitment. NKG2D and presumably CD137 signaling enhances the cytotoxicity of NK cells. (B) In atherosclerotic lesions, PRR and CD137L signaling together results in the production of proinflammatory cytokines and chemokines, while TCR and CD137 signaling in activated T cells leads to IFN-γ production. These immune mediators contribute to chronic inflammation in atherosclerotic lesions. Abbreviations: DAMP, damage-associated molecular patterns; IFN-γ, Interferon-γ; HMGB1, high-mobility group box 1; NK cell, Natural Killer cell; NKG2D, Natural killer group 2, member D; PRR, pattern recognition receptor; TCR, T cell receptor;. TLR2, Toll-like receptor 2.

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