Russell J L, Golub E S
Proc Natl Acad Sci U S A. 1978 Dec;75(12):6211-4. doi: 10.1073/pnas.75.12.6211.
Leukemic AKR mouse spleen cells suppress normal AKR anti-sheep erythrocyte antibody responses in vitro. Treatment of leukemic spleen cells with DNase I prior to coculture with normal AKR cells abrogates their suppressive ability. Treatment of leukemic cells with a wide range of DNase I concentrations has no effect on the viability of these cells as measured by incorporation of [(3)H]thymidine or by eosin dye exclusion. When the activating divalent cations required for DNase I action are functionally removed in the enzyme treatment medium by chelation with EDTA, the ability of DNase I to abrogate suppression is abolished. Furthermore, the effects of DNase I in overcoming suppression are not able to be mimicked by trypsin, Pronase, or ribonuclease. These results are consistent with the existence of a population of cells in the leukemic spleen that expresses a form of membrane-associated DNA that functions in the suppression of normal antibody responses. The existence of such a population was shown by treating leukemic spleen cells with anti-single-stranded-DNA and then passing them through an anti-immunoglobulin immunoadsorption column. Approximately 15% of the leukemic cells are retained on the column and can be specifically eluted with the normal immunoglobulin. The cells of this enriched population when cocultured with normal spleen cells exhibit a 10-fold greater suppressive ability than unfractionated cells. Thus, there exists in the spleens of overtly leukemic AKR mice a population of cells expressing a form of DNA on their surfaces that in some manner is necessary for immunosuppression.
白血病AKR小鼠脾细胞在体外可抑制正常AKR小鼠对绵羊红细胞的抗体反应。在与正常AKR细胞共培养之前,用DNA酶I处理白血病脾细胞可消除其抑制能力。用一系列不同浓度的DNA酶I处理白血病细胞,通过[(3)H]胸腺嘧啶掺入法或伊红染料排斥法检测,对这些细胞的活力没有影响。当通过与EDTA螯合在酶处理培养基中功能性去除DNA酶I作用所需的激活二价阳离子时,DNA酶I消除抑制的能力就会丧失。此外,胰蛋白酶、链霉蛋白酶或核糖核酸酶无法模拟DNA酶I克服抑制的作用。这些结果与白血病脾中存在一群细胞一致,这群细胞表达一种与膜相关的DNA形式,其在抑制正常抗体反应中发挥作用。通过用抗单链DNA处理白血病脾细胞,然后使其通过抗免疫球蛋白免疫吸附柱,证明了这群细胞的存在。大约15%的白血病细胞保留在柱上,可用正常免疫球蛋白特异性洗脱。将这群富集细胞与正常脾细胞共培养时,其抑制能力比未分离的细胞高10倍。因此,在明显白血病的AKR小鼠脾脏中存在一群细胞,其表面表达一种DNA形式,这种DNA形式在某种程度上对免疫抑制是必需的。