Journal List > J Korean Soc Transplant > v.28(3) > 1034423

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

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.

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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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