Priebe T, Ruiz L, Nelson J A
Department of Experimental Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cell Immunol. 1990 Oct 15;130(2):513-9. doi: 10.1016/0008-8749(90)90291-x.
Previous results from this laboratory demonstrated that treatment of mice with the adenosine analog tubercidin (Tub) reduced natural killer (NK) cell activity while stimulating antibody production whereas the deoxyadenosine analog, 2-fluoroadenine arabinoside-5'-monophosphate (FaraAMP), produced opposite effects; i.e., it stimulated NK cell activity at doses that inhibited antibody formation (Cancer Res. 48, 4799, 1988). Since NK cells have been reported to play a suppressor role in immunoglobulin induction, it was hypothesized that the actions of Tub and FaraAMP on antibody production occurred secondary to their opposing effects on NK cells. To test this hypothesis, abilities of these nucleoside analogs to modulate primary antibody response to sheep red blood cells were evaluated in a C57BL/6 mutant mouse lacking NK cell activity (the beige mutation. C57BL/6-bg/bg). As previously found with C3H/He mice. NK cell activity was inhibited (Tub, doses 2-6 mg/kg/day for 3 days) or stimulated (FaraAMP, doses 75-250 mg/kg/day for 3 days) in heterozygous mice C57BL/6-bg/+. In support of the hypothesis, these nucleosides had no effect on primary antibody formation in the homozygous mutant mice at doses that clearly stimulated (Tub) or inhibited (FaraAMP) this immune response in heterozygous C57BL/6-bg/+ animals. This results was corroborated in C57BL/6 wild-type mice by abrogation of NK cell activity using a monoclonal antibody to the NK cell surface glycophisingolipid, ganglio-n-tetraosylceramide. We conclude that under the conditions of drug administration, modulation of primary antibody formation by Tub and FaraAMP in mice occurs indirectly via NK cells. Similar experiments using the potent ADA inhibitor, deoxycoformycin, indicated that its enhancement of primary antibody formation is independent of NK cell activity.
本实验室先前的研究结果表明，用腺苷类似物结核菌素（Tub）处理小鼠会降低自然杀伤（NK）细胞活性，同时刺激抗体产生，而脱氧腺苷类似物2-氟阿拉伯糖腺苷-5'-单磷酸（FaraAMP）则产生相反的效果；即，它在抑制抗体形成的剂量下刺激NK细胞活性（《癌症研究》48, 4799, 1988）。由于有报道称NK细胞在免疫球蛋白诱导中起抑制作用，因此推测Tub和FaraAMP对抗体产生的作用是继发于它们对NK细胞的相反作用。为了验证这一假设，在缺乏NK细胞活性的C57BL/6突变小鼠（米色突变，C57BL/6-bg/bg）中评估了这些核苷类似物调节对绵羊红细胞的初次抗体反应的能力。如先前在C3H/He小鼠中所发现的那样。在杂合子小鼠C57BL/6-bg/+中，NK细胞活性被抑制（Tub，剂量为2 - 6 mg/kg/天，持续3天）或被刺激（FaraAMP，剂量为75 - 250 mg/kg/天，持续3天）。支持这一假设的是，这些核苷在杂合子C57BL/6-bg/+动物中明显刺激（Tub）或抑制（FaraAMP）这种免疫反应的剂量下，对纯合突变小鼠的初次抗体形成没有影响。使用抗NK细胞表面糖鞘脂神经节苷脂-n-四糖神经酰胺的单克隆抗体消除NK细胞活性，在C57BL/6野生型小鼠中证实了这一结果。我们得出结论，在给药条件下，Tub和FaraAMP对小鼠初次抗体形成的调节是通过NK细胞间接发生的。使用强效腺苷脱氨酶（ADA）抑制剂脱氧助间型霉素进行的类似实验表明，其对初次抗体形成的增强作用与NK细胞活性无关。
