Helfand S C, Modiano J F, Moore P F, Soergel S A, MacWilliams P S, Dubielzig R D, Hank J A, Gelfand E W, Sondel P M
School of Veterinary Medicine, Department of Medical Sciences, University of Wisconsin-Madison 53706, USA.
Blood. 1995 Jul 15;86(2):636-45.
We identified a dog with large granular lymphocytic leukemia and cutaneous lymphoma that exhibited constitutive expression of interleukin-2 (IL-2) receptors by the leukemic peripheral blood lymphocytes. The leukemic cells phenotypically resembled natural killer (NK) cells, and their surface IL-2 receptors were functional, as determined by the capacity to bind human recombinant IL-2 with high-affinity resulting in the transduction of proliferation signals and in the development of lymphokine-activated killer cell activity. These cells produced IL-2 spontaneously, and they may have maintained their proliferative state through an IL-2-dependent autocrine growth pathway. Our results indicate that neoplastic lymphocytes of syndromes that involve circulating leukemic cells with dermotropism can originate from NK-like cells. Additionally, the data also suggest that proliferative conditions such as these may be the result of the aberrant production of IL-2. Further, this case illustrates the potential for the use of hematopoietic malignancies in the dog as a suitable animal model for immune targeting of IL-2 receptors as a novel treatment approach for similar malignancies of human beings.
我们鉴定出一只患有大颗粒淋巴细胞白血病和皮肤淋巴瘤的犬，其白血病外周血淋巴细胞组成性表达白细胞介素-2（IL-2）受体。白血病细胞在表型上类似于自然杀伤（NK）细胞，并且其表面IL-2受体具有功能，这是通过高亲和力结合人重组IL-2的能力来确定的，该能力导致增殖信号的转导以及淋巴因子激活的杀伤细胞活性的发展。这些细胞自发产生IL-2，并且它们可能通过IL-2依赖性自分泌生长途径维持其增殖状态。我们的结果表明，涉及具有向皮肤性的循环白血病细胞的综合征的肿瘤性淋巴细胞可能起源于NK样细胞。此外，数据还表明，此类增殖状况可能是IL-2异常产生的结果。此外，该病例说明了将犬的造血系统恶性肿瘤用作针对IL-2受体进行免疫靶向的合适动物模型的潜力，这是一种针对人类类似恶性肿瘤的新型治疗方法。
