T-cell activation via CD26 and caveolin-1 in rheumatoid synovium.
T-cell activation via CD26 and caveolin-1 in rheumatoid synovium.
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DOI：
10.1007/s10165-005-0452-4
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发表时间：
2006
影响因子：
2.2
通讯作者：
中科院分区：
文献类型：
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CD26是一种T细胞共刺激分子，胞外区具有二肽基肽酶IV(DPPIV)活性。我们以前曾报道，重组可溶性CD26能增强破伤风类毒素(TT)诱导的外周血T细胞增殖。最近，我们发现CD26与小凹蛋白-1结合在抗原提呈细胞(APC)上，CD26的201-211位残基与630位丝氨酸催化残基一起构成CD26/DPPIV的口袋结构，有助于与小凹-1支架结构域结合。此外，CD26-小窝蛋白-1与TT负载的单核细胞相互作用后，小窝蛋白-1被磷酸化，并与核因子-κB激活相连，随后CD86上调。免疫组织化学研究显示CD26+T细胞在类风湿滑膜下层区域有CD26+T细胞的浸润，类风湿滑膜血管和滑膜细胞中有小凹-1的高表达。综上所述，这些结果有力地表明，CD26-avolin-1相互作用在TT负载的APC上CD86的上调以及随后与T细胞上的CD28的结合中发挥作用，从而导致抗原特异性T细胞的激活，如类风湿关节炎的T细胞介导的抗原特异性反应。
CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region. We previously reported that recombinant soluble CD26 enhances peripheral blood T-cell proliferation induced by the recall antigen tetanus toxoid (TT). Recently, we demonstrated that CD26 binds caveolin-1 on antigen-presenting cell (APC), and that residues 201–211 of CD26 along with the serine catalytic site at residue 630, which constitute a pocket structure of CD26/DPPIV, contribute to binding to caveolin-1 scaffolding domain. In addition, following CD26–caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, with linkage to NF-κB activation, followed by upregulation of CD86. Finally, reduced caveolin-1 expression on APC inhibits CD26-mediated CD86 upregulation and abrogates CD26 effect on TT-induced T-cell proliferation, and immunohistochemical studies revealed an infiltration of CD26+ T cells in the sublining region of rheumatoid synovium and high expression of caveolin-1 in the increased vasculature and synoviocytes of the rheumatoid synovium. Taken together, these results strongly suggest that CD26–cavolin-1 interaction plays a role in the upregulation of CD86 on TT-loaded APC and subsequent engagement with CD28 on T cells, leading to antigen-specific T-cell activation such as the T-cell-mediated antigen-specific response in rheumatoid arthritis.