Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia.
Blood. 2012 Sep 6;120(10):2055-63. doi: 10.1182/blood-2012-03-416792. Epub 2012 Jun 15.
The transfer of membrane proteins between cells during contact, known as trogocytosis, can create novel cells with a unique phenotype and altered function. We demonstrate that trogocytosis is more common in multiple myeloma (MM) than chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia; that T cells are more probable to be recipients than B or natural killer cells; that trogocytosis occurs independently of either the T-cell receptor or HLA compatibility; and that after trogocytosis, T cells with acquired antigens can become novel regulators of T-cell proliferation. We screened 168 patients with MM and found that CD86 and human leukocyte antigen G (HLA-G) were antigens commonly acquired by T cells from malignant plasma cells. CD3+ CD86acq+ and CD3+ HLA-Gacq+ cells were more prevalent in bone marrow than peripheral blood samples. The presence of either CD86 or HLA-G on malignant plasma cells was associated with a poor prognosis. CD38++ side population cells expressed HLA-G, suggesting that these putative myeloma stem cells could generate immune tolerance. HLA-G+ T cells had a regulatory potency similar to natural Tregs, thus providing another novel mechanism for MM to avoid effective immune surveillance.
细胞接触过程中膜蛋白在细胞间的转移,即细胞吞噬作用,可形成具有独特表型和功能改变的新型细胞。我们证实细胞吞噬作用在多发性骨髓瘤(MM)中比慢性淋巴细胞白血病和华氏巨球蛋白血症更为常见;T 细胞比 B 细胞或自然杀伤细胞更有可能成为受体;细胞吞噬作用独立于 T 细胞受体或 HLA 相容性;在细胞吞噬作用后,获得抗原的 T 细胞可成为 T 细胞增殖的新型调节剂。我们对 168 例 MM 患者进行了筛查,发现 CD86 和人白细胞抗原 G(HLA-G)是 T 细胞从恶性浆细胞获得的常见抗原。骨髓中 CD3+CD86acq+和 CD3+HLA-Gacq+细胞比外周血样本更为常见。恶性浆细胞上存在 CD86 或 HLA-G 与预后不良相关。CD38++侧群细胞表达 HLA-G,提示这些假定的骨髓瘤干细胞可能产生免疫耐受。HLA-G+T 细胞具有与天然 Treg 相似的调节潜能,从而为 MM 逃避有效免疫监测提供了另一种新机制。