Volume 19, No 7, Jul 2009

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 19 Issue 7, July 2009: 816-827

ORIGINAL ARTICLES

Novel function of perforin in negatively regulating CD4⁺ T cell activation by affecting calcium signaling

Enguang Bi¹, Chunjian Huang¹, Yu Hu¹, Xiaodong Wu¹, Weiwen Deng¹, Guomei Lin¹, Zhiduo Liu¹, Lin Tian¹, Shuhui Sun², Kairui Mao¹, Jia Zou¹, Yuhan Zheng¹ and Bing Sun^1,3

¹Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China

²Fudan University School of Medicine, Shanghai 200032, China

³Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025, China Correspondence: Bing Sun,(bsun@sibs.ac.cn)

Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic T lymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4⁺ T cell function remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4⁺ T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell proliferation and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD4⁺ T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFAT1. Our results indicate that perforin plays a negative role in regulating CD4⁺ T cell activation and immune response by affecting TCR-dependent Ca²⁺ signaling.

Cell Research (2009) 19:816-827. doi: 10.1038/cr.2009.32; published online 17 March 2009

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