GUT INJURY IN MOUSE GRAFT-VERSUS-HOST REACTION - STUDY OF ITS OCCURRENCE AND MECHANISMS
GUT INJURY IN MOUSE GRAFT-VERSUS-HOST REACTION - STUDY OF ITS OCCURRENCE AND MECHANISMS
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DOI：
10.1172/jci112474
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发表时间：
1986-05-01
影响因子：
15.9
通讯作者：
VASSALLI, P
中科院分区：
文献类型：
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作者：
GUYGRAND, D;VASSALLI, P
在多种小鼠移植物抗宿主反应（GVHR）条件下，研究了肠道病变的发生、性质和发病机制，结合以下性质的变化：F1宿主（新生或成年，正常或致命辐照），注射的亲代T细胞（混合或选择的Ly2+或L3T4+细胞亚群），抗原刺激（半同种异体或仅限于I类或II类MHC位点）。得出以下结论：(a)三种肠道改变总是相关的：(i)供体T细胞浸润，主要在隐窝区；（ii）上皮更新加速；（iii）上皮Ia表达增加。(b)最初的事件是t细胞浸润，这是由Peyer斑块内的刺激引起的，然后是循环流动，即迁移到胸导管，然后播种到整个肠道粘膜。(c) Lyt2+和L3T4+细胞都能浸润肠壁，特定亚群浸润的程度取决于(i)供体细胞在胸导管中循环的能力（L3T4+细胞较高），然后回到肠道（Lyt2+细胞高得多）和（ii）控制每个供体细胞亚群增殖程度的同种抗原刺激的性质。(d)两种供体t细胞亚群均可诱导肠上皮损伤，但对于相当数量的浸润细胞，L3T4+细胞诱导的病变更多。(e)当抗原刺激仅限于I类或I类MHC位点时，肠道GVHR更容易在II类MHC差异中被激发，II类MHC差异优先刺激L3T4+供体细胞。(f)。上皮损伤的主要机制不是直接的细胞毒性，而更可能是淋巴因子的释放。
The occurrence, nature, and pathogenesis of intestinal lesions were studied in a number of graft vs. host reaction (GVHR) conditions in mice, combining variations in the nature of the following: the F1 hosts (newborn or adult, normal or lethally irradiated), the injected parental T cells (mixed or selected subsets of Ly2+ or L3T4+ cells), and the antigenic stimulus (semiallogeneic or restricted to class I or II MHC loci). The following conclusions were drawn: (a) Three gut alterations are always associated: (i) donor T cell infiltration, predominating in the crypt region; (ii) acceleration of the epithelium renewal; and (iii) increased epithelial Ia expression. (b) The initial event is T-cell infiltration, which results from stimulation within the Peyer patches followed by cyclic traffic, i.e., migration into the thoracic duct and then seeding to the whole gut mucosa. (c) Both Lyt2+ and L3T4+ cells can infiltrate the gut wall, the extent of the infiltration by a given subset depending upon (i) the capacity of the donor blasts to circulate in the thoracic duct (higher for L3T4+) and then to home in the gut (much higher for Lyt2+ blasts) and (ii) the nature of the alloantigenic stimulation that governs the extent of each donor subset proliferation. (d) Both donor T-cell subsets can induce gut epithelial damage, but for a comparable amount of infiltrating cells, L3T4+ cells induce more lesions. (e) When the antigenic stimulation is restricted to class I or class I MHC loci, gut GVHR is much more easily elicited across class II MHC differences, which stimulate preferentially L3T4+ donor cells. (f). The main mechanism of epithelial damage is not direct cytotoxicity, but more probably lymphokine(s) release.