Van Buren C T, Kulkarni A D, Fanslow W C, Rudolph F B
Transplantation. 1985 Dec;40(6):694-7. doi: 10.1097/00007890-198512000-00024.
Previous investigations have revealed that dietary nucleotide restriction delays the onset of primary murine cardiac allograft rejection and acute graft-versus-host disease followed H-2-incompatible bone marrow transplantation, suppresses sensitization to intradermally injected antigens and suppresses in vivo and in vitro lymphocyte proliferation to alloantigen or lectin stimulation. To determine the mechanisms responsible for these phenomena, BALB/c mice were placed on chow (F), nucleotide free (NF) diet, or NF diet supplemented with 0.25% RNA (NFR), with 0.6% adenine (NFA), or with 0.06% uracil (NFU). Following four weeks of dietary equilibrium, splenic lymphocytes harvested from naive or immunostimulated mice in the various dietary groups were stained with monoclonal antibodies directed Lyt 1, Lyt 2, 3, or surface mouse immunoglobulin (IgG) surface markers. While naive animals demonstrated no differences in lymphocyte subpopulations between groups, following complete Freund's adjuvant (CFA) stimulation, splenic lymphocytes for NF mice demonstrated 27.3 +/- 1.7% Lyt 1+ cells compared with F (32.6 +/- .04%) and NFR mice (33.2 +/- 1.2%) (P less than 0.02). Restriction of dietary nucleotides affected not only phenotypes of T lymphocytes, but also T cell function. Following conconavalin A stimulation of irradiated splenic lymphocytes, IL-2 production was decreased in NF mice compared with the F control group (P less than 0.01). The RNA-repleted diet maintained normal IL-2 production, while addition of adenine or uracil alone did not. Finally, NF diets adversely affected host resistance to the opportunistic pathogen Candida albicans. Following inoculation with 0.25 X 10(6) organisms NF or NFA-fed hosts succumbed more rapidly than F, NFR, or NFU fed hosts (P less than 0.001). These data suggest that helper/inducer T lymphocytes require exogenous nucleotides to respond normally following immune stimulation. Uracil may be the critical substrate, based upon the studies of Candida resistance. By understanding the metabolic basis of NFD-induced immunosuppression, the role of dietary nucleotides in combatting infection and alloantigen rejection can be more clearly defined.
先前的研究表明，饮食中核苷酸限制可延缓原发性小鼠心脏同种异体移植排斥反应的发生，并延缓H-2不相容骨髓移植后急性移植物抗宿主病的发生，抑制对皮内注射抗原的致敏作用，并抑制体内和体外淋巴细胞对同种抗原或凝集素刺激的增殖。为了确定导致这些现象的机制，将BALB/c小鼠置于普通饲料（F）、无核苷酸（NF）饮食、或补充有0.25%RNA（NFR）、0.6%腺嘌呤（NFA）或0.06%尿嘧啶（NFU）的NF饮食中。经过四周的饮食均衡后，从不同饮食组的未免疫或免疫刺激小鼠中收获的脾淋巴细胞用针对Lyt 1、Lyt 2、3或表面小鼠免疫球蛋白（IgG）表面标志物的单克隆抗体进行染色。虽然未免疫动物在各组之间的淋巴细胞亚群中未显示出差异，但在完全弗氏佐剂（CFA）刺激后，NF小鼠的脾淋巴细胞显示Lyt 1+细胞为27.3±1.7%，而F组（32.6±0.04%）和NFR组小鼠（33.2±1.2%）（P<0.02）。饮食中核苷酸的限制不仅影响T淋巴细胞的表型，还影响T细胞功能。在刀豆球蛋白A刺激照射后的脾淋巴细胞后，与F对照组相比，NF小鼠的IL-2产生减少（P<0.01）。补充RNA的饮食维持了正常的IL-2产生，而单独添加腺嘌呤或尿嘧啶则没有。最后，NF饮食对宿主抵抗机会性病原体白色念珠菌的能力产生不利影响。在用0.25×10⁶个生物体接种后，NF或NFA喂养的宿主比F、NFR或NFU喂养的宿主更快死亡（P<0.001）。这些数据表明，辅助/诱导性T淋巴细胞在免疫刺激后需要外源性核苷酸才能正常反应。基于对念珠菌抗性的研究，尿嘧啶可能是关键底物。通过了解NFD诱导的免疫抑制的代谢基础，可以更清楚地界定饮食中核苷酸在对抗感染和同种抗原排斥中的作用。
