Basic study of molecular target therapy for autoimmune diseases and immune deficiency diseases based on CD26

CD26是一种T细胞活化抗原，含有二肽基肽酶IV活性，并与腺苷脱氨酶结合。我们研究了CD26在脐血T细胞活化和信号转导中的作用。发现脐血T细胞(CBTCs)和外周血T细胞(PBTCs)表达CD26的水平不同，CD26 CD45RA()CBTCs与CD26(CD45RA())PBTCs不同。此外，CD26在CBTCs中的伴生作用不如在PBTCs中明显。我们还发现CD26在CBTCs中诱导的T细胞受体信号分子、淋巴T细胞蛋白酪氨酸激酶(Lck)、Zeta相关蛋白70(ZAP-70)、T细胞受体Zeta(TCRzeta)和T细胞激活物(LAT)连接物的磷酸化程度低于PBTCs。此外，CD26分子与CD45RA分子结合在CBTCs的脂筏外。我们的结果提示CD26与CD45RA在脂筏外的强物理连接可能是…的原因CD26激活T细胞信号的减弱，可能是脐血移植免疫反应不成熟和严重移植物抗宿主病发生率低的原因。我们先前报道了重组可溶性CD26促进了Recall抗原破伤风类毒素(TT)诱导的T细胞增殖。然而，这种增强的机制尚未阐明。我们现在证明CD26与抗原提呈细胞上的小凹-1结合，并且CD26的201-211残基以及630位的丝氨酸催化位点有助于与小窝-1支架结构域的结合。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，从而激活了核因子-kappaB，随后上调了CD86。最后，减少单核细胞上小凹蛋白-1的表达可抑制CD26介导的CD86上调，并取消CD26对TT诱导的T细胞增殖的影响。综上所述，这些结果有力地表明，CD26-小窝蛋白-1的相互作用在单核细胞上CD86的上调以及随后与T细胞上的CD28结合导致抗原特异性T细胞激活中起作用。较少

CD26 is a T-cell activation antigen that contains dipeptidyl peptidase IV activity and binds adenosine deaminase. We investigate the role of CD26 in cord blood T-cell activation and signal transduction. We demonstrated that different expression levels of CD26 were observed between cord blood T cells(CBTCs) and peripheral blood T cells(PBTCs) and that CD26(+)CD45RA(+) CBTCs were different compared with CD26(+)CD45RA(+) PBTCs. Moreover, the comitogenic effect of CD26 was not as pronounced in CBTCs as in PBTCs. We also showed that CD26 cross-linking induced less phosphorylation of T-cell receptor-signaling molecules, lymphoid T-cell protein tyrosine kinase(Lck), zeta-associated protein 70(ZAP-70), T-cell receptor zeta(TCRzeta), and linker for activator of T cells(LAT) in CBTCs than in PBTCs. Furthermore, CD26 molecules associated with CD45RA molecules outside lipid rafts in CBTCs. Our results suggest that strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible f … More or the attenuation of T-cell activation signaling through CD26, which may be responsible for immature immune response and the low incidence of severe graft-versus-host disease in cord blood transplantation.We previously reported that recombinant soluble CD26 enhanced T cell proliferation induced by the recall antigen tetanus toxoid(TT). However, the mechanism involved in this enhancement is not yet elucidated. We now demonstrate that CD26 binds Caveolin-1 on antigen-presenting cells, and that residues 201-211 of CD26 along with the serine catalytic site at residue 630 contribute to binding to caveolin-1 scaffolding domain. In addition, after CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, which links to activate NF-kappaB, followed by up-regulation of CD86. Finally, reduced caveolin-1 expression on monocytes inhibits CD26-mediated CD86 up-regulation and abrogates CD26 effect on TT-induced T cell proliferation. Taken together, these results strongly suggest that CD26-caveolin-1 interaction plays a role in the up-regulation of CD86 on monocytes and subsequent engagement with CD28 on T cells, leading to antigen-specific T cell activation. Less