Huang Yin, Chen Zhi, Zhou Cheng, Yao Hangping, Li Minwei, Xu Chenghuai
Institute of Infectious Diseases, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79 Hangzhou 310003, People's Republic of China.
Int Immunopharmacol. 2004 Apr;4(4):539-46. doi: 10.1016/j.intimp.2004.02.008.
Thymosin alpha 1 (Talpha1) has immunomodulatory effects on T-cells, NK-cells and macrophages, but its action on dendritic cells (DCs), which are recognized as the sole professional antigen presenting cells (APCs) capable of priming naïve T-cells, is poorly understood. In this study, the effect of Talpha1 in vitro on murine bone marrow-derived DCs (BMDCs) maturation, differentiation, and function with or without tumor necrosis factor-alpha (TNF-alpha), which is one of the important inflammatory parameters, has been investigated. We have shown, through flow cytometry, ELISA and mixed leukocyte reaction (MLR), that Talpha1 promoted CD4-expressed DC differentiation and the expression of activation markers, but did not influence IL-12 production and T cell-stimulatory capacity of DCs in the absence of TNFalpha during BMDCs maturation. Furthermore, in the presence of TNF-alpha, Talpha1 has been shown not only to promote the expression of CD4 on MHC class II+ DCs and enhance the up-regulated levels of mature markers induced by TNF-alpha, but also to suppress the up-regulated IL-12 production. Particularly, thus effects seen were obvious at pharmacological Talpha1 concentrations. However, Talpha1 did not inhibit TNF-alpha-induced T-cell stimulating function of DCs. This is the first reported example of a direct Talpha1-DC interaction and suggests a mechanism by which Talpha1 may in part affect T-cell responses by acting at the DC level and it may play an important role in the modulation of the local inflammatory responses in vivo.
胸腺肽α1（Tα1）对T细胞、自然杀伤细胞（NK细胞）和巨噬细胞具有免疫调节作用，但其对树突状细胞（DC）的作用却鲜为人知，而DC是唯一能够激活初始T细胞的专职抗原呈递细胞（APC）。在本研究中，我们探讨了Tα1在体外对小鼠骨髓来源的DC（BMDC）成熟、分化及功能的影响，同时研究了其在有或无肿瘤坏死因子-α（TNF-α，一种重要的炎症参数）存在时的作用。通过流式细胞术、酶联免疫吸附测定（ELISA）和混合淋巴细胞反应（MLR），我们发现，在BMDC成熟过程中，当不存在TNF-α时，Tα1可促进表达CD4的DC分化及激活标志物的表达，但不影响DC的白细胞介素-12（IL-12）产生及T细胞刺激能力。此外，在存在TNF-α的情况下，Tα1不仅可促进MHC II类+DC上CD4的表达，并增强TNF-α诱导的成熟标志物上调水平，还可抑制IL-12的上调产生。特别地，这些作用在药理学浓度的Tα1下较为明显。然而，Tα1并未抑制TNF-α诱导的DC的T细胞刺激功能。这是首次报道的Tα1与DC直接相互作用的实例，提示Tα1可能通过作用于DC水平部分影响T细胞反应的机制，且其可能在体内局部炎症反应的调节中发挥重要作用。
