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，具有二肽基肽酶IV活性并结合腺苷脱氨酶。我们研究了CD26在脐带血t细胞活化和信号转导中的作用。我们证实CD26在脐带血T细胞（CBTCs）和外周血T细胞（PBTCs）中表达水平不同，CD26(+)CD45RA(+) CBTCs与CD26(+)CD45RA(+) PBTCs之间表达水平不同。此外，CD26在cbtc中的致comitogenic effect不像在pbtc中那么明显。我们还发现CD26交联在cbtc中诱导的T细胞受体信号分子、淋巴样T细胞蛋白酪氨酸激酶（Lck）、ζ相关蛋白70（ZAP-70）、T细胞受体zeta（TCRzeta）和T细胞激活物连接子（LAT）的磷酸化程度低于pbtc。此外，CD26分子与cbtc脂筏外的CD45RA分子相关。我们的研究结果表明，CD26与脂质筏外的CD45RA的强物理联系可能是导致t细胞激活信号通过CD26衰减的原因，这可能是脐带血移植中不成熟免疫反应和严重移植物抗宿主病发生率低的原因。我们以前报道过重组可溶性CD26增强由回忆抗原破伤风类毒素（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在抗原呈递细胞上结合Caveolin-1，并且CD26的残基201-211以及残基630的丝氨酸催化位点有助于结合Caveolin-1支架结构域。此外，CD26-caveolin-1在tt负载的单核细胞上相互作用后，caveolin-1被磷酸化，其连接激活NF-kappaB，随后CD86上调。最后，单核细胞caveolin-1表达的降低抑制了CD26介导的CD86上调，并消除了CD26对tt诱导的T细胞增殖的作用。综上所述，这些结果强烈表明CD26-caveolin-1相互作用在单核细胞上CD86的上调以及随后与T细胞上CD28的相互作用中发挥作用，从而导致抗原特异性T细胞活化。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