International Journal of Medical Sciences

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16 December 2017

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Int J Med Sci 2015; 12(8):650-654. doi:10.7150/ijms.12304

Research Paper

Regulatory and Effector Helper T-Cell Profile after Nerve Xenografting in the Toll-Like Receptor-Deficient Mice

Cheng-Shyuan Rau1*, Ming-Wei Lin2*, Shao-Chun Wu3*, Yi-Chan Wu2, Tsu-Hsiang Lu2, Siou-Ling Tzeng2, Yi-Chun Chen2, Chia-Jung Wu2, Ching-Hua Hsieh2✉

1. Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
2. Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
3. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
*These authors contributed equally to this work

Abstract

Introduction: The balance between regulatory T cells (Tregs) and effector T help cells (Th cells) is critical for the control of adaptive immune response during nerve transplantation. However, whether the homeostasis of immune regulation between Tregs and Th cells requires toll-like receptor (TLR) signaling is unclear. The aim of this study is to profile the distribution of spleen Tregs and Th cells in a mouse model of nerve xenografting in the TLR2 and NF-κB gene knockout mice.

Methods: The sciatic nerve was taken from a SD rat or an allogeneic mouse and transplanted to a right back leg of recipient C57BL/6, TLR2-/-, or NF-κB-/- mice by subcutaneous transplantation. After 7 days, the T lymphocytes were then isolated from spleen, stained with phenotyping kits, and analyzed by flow cytometry.

Results: The results showed that Tregs were decreased after nerve xenografting in the recipient C57BL/6 mouse. In addition, nerve xenografting also increased the Th1 and Th17 but not the Th2 cell populations. In contrast, amelioration of the Tregs elimination was found in TLR2-/- and NF-κB-/- mice after transplantation of the nerve xenograft. Moreover, the mice lacking TLR2 or NF-κB showed attenuation of the increase in Th1 and Th17 cells after nerve xenografting.

Conclusions: TLR signaling is involved in T cell population regulation during tissue transplantation. Knock-out of TLR2 and NF-κB prevented Tregs elimination and inhibited Th1- and Th17-driven immune response after nerve xenografting. This study highlighted the potential of inhibiting TLR signaling to modulate T cell-mediated immune regulation to facilitate tolerance to nerve transplantation.

Keywords: Nerve xenografting, Toll-like receptor (TLR), Regulatory T cells (Tregs), T help cells (Th cells)

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How to cite this article:
Rau CS, Lin MW, Wu SC, Wu YC, Lu TH, Tzeng SL, Chen YC, Wu CJ, Hsieh CH. Regulatory and Effector Helper T-Cell Profile after Nerve Xenografting in the Toll-Like Receptor-Deficient Mice. Int J Med Sci 2015; 12(8):650-654. doi:10.7150/ijms.12304. Available from http://www.medsci.org/v12p0650.htm