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

CD 26是一种T细胞活化抗原，含有二肽基肽酶IV活性并结合腺苷脱氨酶。我们研究CD 26在脐带血T细胞活化和信号转导中的作用。结果表明，CD 26在脐血T细胞（CBTC）和外周血T细胞（PBTC）中的表达水平不同，CD 26（+）CD 45 RA（+）CBTC与CD 26（+）CD 45 RA（+）PBTC的表达水平不同。此外，CD 26在CBTC中的共致有丝分裂作用不如在PBMC中那么明显。我们还发现，CD 26交联诱导CBTC中T细胞受体信号传导分子、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（TCR zeta）和T细胞激活因子连接子（LAT）的磷酸化程度低于PBMC。此外，CD 26分子与CBTC中脂筏外的CD 45 RA分子缔合。我们的研究结果表明，CD 26和CD 45 RA在脂筏外的强物理连接可能是导致细胞凋亡的原因。 关于我们 我们以前报道过重组可溶性CD 26能增强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，CD 26结合的小窝蛋白-1抗原呈递细胞，以及残基201-211的CD 26与丝氨酸催化位点在残基630有助于结合小窝蛋白-1支架结构域。此外，在TT负载的单核细胞上的CD 26-小窝蛋白-1相互作用后，小窝蛋白-1被磷酸化，其连接以激活NF-κ B，随后上调CD 86。最后，单核细胞上小窝蛋白-1表达的降低抑制了CD 26介导的CD 86上调，并消除了CD 26对TT诱导的T细胞增殖的作用。总之，这些结果强烈表明，CD 26-小窝蛋白-1相互作用在单核细胞上的CD 86的上调和随后与T细胞上的CD 28的接合中起作用，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