Bleesing J J, Brown M R, Dale J K, Straus S E, Lenardo M J, Puck J M, Atkinson T P, Fleisher T A
Immunology Service, Warren G. Magnuson Clinical Center, Bethesda, Maryland 20892, USA.
Clin Immunol. 2001 Sep;100(3):314-24. doi: 10.1006/clim.2001.5069.
Autoimmune lymphoproliferative syndrome (ALPS), caused by inherited defects in apoptosis secondary to mutations in genes encoding Fas/CD95/APO-1 and Fas ligand (Fasl)/CD95L, is characterized by nonmalignant lymphadenopathy and splenomegaly, increased T cell receptor alpha/beta(+) CD4(-)CD8(-) T cells (alpha/beta(+) double-negative T cells [alpha/beta(+)-DNT cells]), autoimmunity, hypergammaglobulinemia, and cytokine abnormalities. The alpha/beta(+)-DNT cells are immunophenotypically and functionally similar to alpha/beta(+)-DNT cells that accumulate in lpr and gld mice, which bear genetic mutations in Fas and FasL. In these mice, alpha/beta(+)-DNT cells express the B-cell-specific CD45R isoform B220. We show that alpha/beta(+)-DNT cells of ALPS patients, with either Fas or FasL mutations, also express B220. In addition, also similar to LPR/gLD mice, they have an unusual population of B220-positive CD4(+) T cells. B220 expression, together with our finding of characteristic lectin binding profiles, demonstrates that cell surface O-linked glycoproteins have undergone specific modifications, which may have consequences for lymphocyte trafficking, cell-cell interactions, and access to alternative apoptosis pathways.
自身免疫性淋巴细胞增生综合征（ALPS）由编码Fas/CD95/APO-1和Fas配体（FasL）/CD95L的基因突变继发的凋亡遗传缺陷引起，其特征为非恶性淋巴结病和脾肿大、T细胞受体α/β(+)CD4(-)CD8(-)T细胞（α/β(+)双阴性T细胞[α/β(+)-DNT细胞]）增加、自身免疫、高球蛋白血症和细胞因子异常。α/β(+)-DNT细胞在免疫表型和功能上与在Fas和FasL发生基因突变的lpr和gld小鼠中积累的α/β(+)-DNT细胞相似。在这些小鼠中，α/β(+)-DNT细胞表达B细胞特异性CD同工型B220。我们发现，无论是Fas还是FasL发生突变的ALPS患者的α/β(+)-DNT细胞也表达B220。此外，与LPR/gLD小鼠相似，它们还有一群不同寻常的B220阳性CD4(+)T细胞。B220的表达以及我们对特征性凝集素结合谱的发现表明，细胞表面O-连接糖蛋白发生了特定修饰，这可能对淋巴细胞运输、细胞间相互作用以及进入其他凋亡途径产生影响。
