Functional demonstration of intrathymic binding sites and microvascular gates for prothymocytes in irradiated mice
Functional demonstration of intrathymic binding sites and microvascular gates for prothymocytes in irradiated mice
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DOI：
10.1093/intimm/14.3.331
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发表时间：
2002-03-01
影响因子：
4.4
通讯作者：
Goldschneider, I
中科院分区：
文献类型：
--
作者：
Foss, DL;Donskoy, E;Goldschneider, I
定量胸腺内（i.t.）和前胸腺细胞的i.t.过继转移测定显示严格的对数剂量饱和动力学，与有限数量的i.t.过继转移测定一致。结合位点（微环境小生境）。这一推论得到了支持，在这里的竞争性拮抗作用服从一对一受体占用动力学在建立胸腺嵌合体在照射的成年小鼠。初级和次级转移实验的结果表明，造血前体（i）进入特定的i.t.在注射后4和24小时之间的小生境，（ii）与随后引入的前体可逆地竞争，（iii）在5-7天内建立不可克服的竞争，（iv）在增殖性扩增之前通过胸腺细胞生成的初始阶段成熟，和（v）在进入后7和14天之间空出小生境。结果还表明，在未照射小鼠，前胸腺细胞输入照射小鼠是一个门控现象。静脉注射无法，但不是I.T.-，注射骨髓（BM）细胞以诱导胸腺嵌合体，当在初次注射和通过i. v.注射BM细胞以诱导与循环宿主前胸腺细胞竞争的胸腺嵌合体。门关闭是对数剂量反应性的，并且可以通过单侧i.t.注射，而发生双侧的门开放直到大多数前胸腺细胞的小生境被腾空才开始。因此，我们认为存在一系列相关的微血管门和微环境的小生境，共同作用，以调节前胸腺细胞的进口和早期胸腺细胞分化。
Quantitative intrathymic (i.t.) and i.v. adoptive transfer assays for prothymocytes show strict log dose saturation kinetics, consistent with a finite number of i.t. binding sites (microenvironmental niches). This inference is supported here by demonstration of competitive antagonism obeying one-on-one receptor occupancy kinetics during the establishment of thymic chimerism in irradiated adult mice. The results of primary and secondary transfer experiments suggested that hematogenous precursors (i) enter specific i.t. niches between 4 and 24 h after injection, (ii) compete reversibly with subsequently introduced precursors, (iii) establish unsurmountable competition within 5-7 days, (iv) mature through the initial stages of thymocytopoiesis preceding proliferative expansion, and (v) vacate the niches between 7 and 14 days after entry. The results also suggested that, as in non-irradiated mice, prothymocyte importation in irradiated mice is a gated phenomenon. Gate closure was indicated by the inability of i.v.-, but not i.t.-, injected bone marrow (BM) cells to induce thymic chimerism when administered 7-14 days after a primary injection and gate opening by the ability of i.v.-injected BM cells to induce thymic chimerism in competition with circulating host prothymocytes. Gate closing was log dose-responsive and could be induced in individual thymic lobes by unilateral i.t. injection, whereas gate opening, which occurs bilaterally, was not initiated until most of the niches for prothymocytes had been vacated. We therefore posit the existence of a series of associated microvascular gates and microenvironmental niches that act in concert to regulate prothymocyte importation and early thymocyte differentiation.