Wadgymar A, Urmson J, Baumal R, Halloran P F
J Immunol. 1984 Apr;132(4):1826-32.
We induced graft-vs-host disease (GVHD) in mice to determine whether immunologic stimuli could alter renal Ia expression. Two strain combinations were used: B6.C-H-2bm12 into C57BL/6, an I-A mutation difference, and A.SW into A.TL, differing in the I and D regions of H-2. By day 10 after allogeneic reconstitution of lethally irradiated recipients with bone marrow and spleen cells, the recipients had developed acute GVHD, as measured by their spleen to body weight ratio. Histologic examination revealed focal interstitial infiltrates of mononuclear cells in the kidneys. The expression of host Ia in these kidneys was increased up to 10-fold, as measured by absorption, and indirect immunofluorescence indicated that certain renal tubule cells had become strongly positive, suggesting that these were the principal sites of the increase in Ia expression. Similar increases were not observed in donor Ia. Tubule cells may have become Ia positive by passive uptake, or more probably, by the increase of Ia biosynthesis in cells that usually synthesize little or no Ia. Lethal irradiation without reconstitution tended to decrease renal Ia expression, as assessed by absorption and immunofluorescence. The results indicate that renal Ia expression, particularly in renal tubules, can be altered by changes in the immune system, raising the possibility of a role for such altered Ia expression in autoimmune or alloimmune responses involving the kidney.
我们在小鼠中诱发移植物抗宿主病（GVHD），以确定免疫刺激是否能改变肾脏Ia的表达。使用了两种品系组合：将B6.C-H-2bm12移植到C57BL/6中，这是一种I-A突变差异，以及将A.SW移植到A.TL中，它们在H-2的I区和D区存在差异。在用骨髓和脾细胞对致死性照射的受体进行同种异体重建后第10天，通过脾与体重比测量发现受体发生了急性GVHD。组织学检查显示肾脏中有局灶性单核细胞间质浸润。通过吸收法测量，这些肾脏中宿主Ia的表达增加了10倍，间接免疫荧光表明某些肾小管细胞呈强阳性，提示这些是Ia表达增加的主要部位。在供体Ia中未观察到类似的增加。肾小管细胞可能通过被动摄取而变成Ia阳性，或者更可能是通过通常很少合成或不合成Ia的细胞中Ia生物合成的增加。通过吸收法和免疫荧光评估，未进行重建的致死性照射往往会降低肾脏Ia的表达。结果表明，肾脏Ia的表达，特别是在肾小管中的表达，可因免疫系统的变化而改变，这增加了这种改变的Ia表达在涉及肾脏的自身免疫或同种免疫反应中发挥作用的可能性。
