Claus Jonathan A, Brady Michael T, Lee Jaewoo, Donohue Kathleen A, Sait Sheila N, Ferrone Soldano, Wetzler Meir
Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Cancer Immunol Immunother. 2006 Feb;55(2):160-5. doi: 10.1007/s00262-005-0012-y. Epub 2005 Jul 12.
Dendritic-like cells from t(9;22) acute lymphoblastic leukemia (ALL) blasts can activate T cells, while the original unmodified leukemic blasts cannot. To determine whether these functional differences were associated with differences in antigen-processing machinery (APM) component expression, we have measured the level of APM component expression in unmodified blasts and ALL-derived dendritic-like cells. Seven t(9;22) ALL patient samples and one cell line were studied for APM component expression utilizing a unique panel of recently developed monoclonal antibodies and a recently developed intracellular staining technique. In addition, the HLA class I antigen cell surface expression was measured. HLA class I antigens were similarly expressed on the unmodified blasts and on the autologous dendritic-like cells. Intracellular HLA class I antigen and tapasin expression (P=0.03 for both) were upregulated in all t(9;22) ALL-derived dendritic-like cells, in comparison to the unmodified blasts. These results provide a potential mechanism for the ability of t(9;22) ALL-derived dendritic-like cells to induce T-cell activation and, suggest that tapasin upregulation may serve as a marker to standardize and monitor the quality of the dendritic-like cells used in immunotherapy.
来自t(9;22)急性淋巴细胞白血病（ALL）母细胞的树突状样细胞能够激活T细胞，而原始未修饰的白血病母细胞则不能。为了确定这些功能差异是否与抗原加工机制（APM）成分表达的差异相关，我们测量了未修饰母细胞和ALL来源的树突状样细胞中APM成分的表达水平。利用一组最近开发的独特单克隆抗体和一种最近开发的细胞内染色技术，对7例t(9;22) ALL患者样本和1个细胞系进行了APM成分表达研究。此外，还测量了HLA I类抗原的细胞表面表达。HLA I类抗原在未修饰的母细胞和自体树突状样细胞上的表达相似。与未修饰的母细胞相比，所有t(9;22) ALL来源的树突状样细胞中细胞内HLA I类抗原和塔帕辛表达均上调（两者P值均为0.03）。这些结果为t(9;22) ALL来源的树突状样细胞诱导T细胞激活的能力提供了一种潜在机制，并表明塔帕辛上调可能作为一种标志物，用于标准化和监测免疫治疗中使用的树突状样细胞的质量。
