Ni Zhenya, Campbell James J, Niehans Gloria, Walcheck Bruce
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue, St. Paul, MN 55108, USA.
J Immunol. 2006 Oct 1;177(7):4742-8. doi: 10.4049/jimmunol.177.7.4742.
T cells use the vascular adhesion molecules E- and P-selectin to enter inflamed skin. Previous studies have indicated the possibility for diversity in the synthesis of E- and P-selectin glycan ligands by activated T cells due to their different requirements for the O-glycan branching enzyme core 2 beta1,6-N-acetylglucosaminyltransferase I and its independent regulation. It is known that T cell staining by the mAb HECA-452 (referred to as cutaneous lymphocyte-associated Ag (CLA) T cells) correlates with E-selectin binding, yet whether these cells uniformly bind P-selectin is less clear. The mAb CHO-131 and P-selectin binding require a glycan moiety consisting of a sialylated and fucosylated oligosaccharide properly positioned on a core-2 O-glycan. Interestingly, CHO-131 stains a subset of CLA(+) T cells. A direct comparison of the selectin binding capacity of CHO-131(+) and CHO-131(-) CLA(+) T cells revealed a significantly greater P-selectin, but not E-selectin, binding activity by the former subset. Based on the expression of homing and central and effector memory cell markers, CHO-131(+) and CHO-131(-) CLA(+) T cells have an overlapping skin-tropic and memory phenotype. CHO-131(+) T cells were considerably enriched in psoriatic skin, yet, unlike the peripheral blood of healthy individuals, HECA-452 and CHO-131 stained a similar proportion of T cells in the cutaneous lesions, indicating an accumulation advantage by CHO-131(+) T cells. We conclude that the CHO-131(+)CLA(+) T cell subset is enriched in P-selectin binding cells. These findings should provide new insights into the regulation and function of skin homing T cells.
T细胞利用血管粘附分子E-选择素和P-选择素进入炎症皮肤。先前的研究表明,活化的T细胞合成E-选择素和P-选择素聚糖配体可能存在多样性,这是由于它们对O-聚糖分支酶核心2β1,6-N-乙酰葡糖胺基转移酶I有不同需求且其调控独立。已知单克隆抗体HECA-452对T细胞的染色(称为皮肤淋巴细胞相关抗原(CLA)T细胞)与E-选择素结合相关,但这些细胞是否均一地结合P-选择素尚不清楚。单克隆抗体CHO-131与P-选择素结合需要一个由唾液酸化和岩藻糖基化寡糖组成的聚糖部分,该寡糖正确定位在核心2 O-聚糖上。有趣的是,CHO-131可对CLA(+) T细胞的一个亚群进行染色。对CHO-131(+)和CHO-131(-) CLA(+) T细胞的选择素结合能力进行直接比较发现,前一个亚群的P-选择素结合活性显著更高,但E-选择素结合活性并非如此。基于归巢以及中枢和效应记忆细胞标志物的表达,CHO-131(+)和CHO-131(-) CLA(+) T细胞具有重叠的皮肤趋向性和记忆表型。CHO-131(+) T细胞在银屑病皮肤中显著富集,然而,与健康个体的外周血不同,在皮肤病变中HECA-452和CHO-131染色的T细胞比例相似,这表明CHO-131(+) T细胞具有积累优势。我们得出结论,CHO-131(+)CLA(+) T细胞亚群富含P-选择素结合细胞。这些发现应为皮肤归巢T细胞的调控和功能提供新的见解。