Kootstra C J, Sutmuller M, Baelde H J, de Heer E, Bruijn J A
Department of Pathology, Leiden University Hospital, The Netherlands.
J Pathol. 1998 Feb;184(2):219-25. doi: 10.1002/(SICI)1096-9896(199802)184:2<219::AID-PATH990>3.0.CO;2-9.
Mice with chronic graft-versus-host disease (GvHD) induced by injection of DBA/2 lymphocytes into (DBA/2 x C57BL/10) F1 hybrids (DBA/2 GvHD) develop a lupus-like glomerulonephritis with global glomerulosclerosis 12 weeks after induction of the disease. In two other strain combinations with similar H-2 incompatibilities [BALB/c into BALB/c x BL10 (BALB/c GvHD) and BALB.D2 into BALB.D2 x BL10 (BALB.D2 GvHD)], GvHD induction leads to lupus nephritis without global glomerulosclerosis. This study investigated the identity of kidney-infiltrating leukocytes and their involvement in the development of glomerulosclerosis in these three strain combinations. In mice with DBA/2 GvHD, a significant increase in glomerular CD11a-positive cells was found 4 weeks after disease induction. Mice with BALB/c or BALB.D2 GvHD did not show an increase in glomerular CD11a-positive cells at any time point. In the interstitium, CD11a-positive cells were observed 4 weeks after disease induction only in mice with DBA/2 GvHD. In mice with BALB.D2 GvHD, no increase was found in interstitial CD11a-positive cells. In mice with BALB/c GvHD, interstitial CD11a-positive cells were found from week 4 onward. Further immunohistochemical analysis of the glomerular CD11a-positive cells in mice with DBA/2 GvHD showed that these cells were neither polymorphonuclear leukocytes (PMN), nor CD3-positive (T cells), B220-positive (B cells), or F4/80-positive (macrophages). They were all CD45-positive (leukocytes) and MHC class II-positive. In conclusion, we have shown in this model of chronic lupus nephritis that glomerular influx of as yet unidentified CD11a-positive leukocytes is associated with the development of glomerulosclerosis.
通过向（DBA/2×C57BL/10）F1杂种小鼠（DBA/2移植物抗宿主病）注射DBA/2淋巴细胞诱导出慢性移植物抗宿主病（GvHD）的小鼠，在疾病诱导12周后会发生伴有全球性肾小球硬化的狼疮样肾小球肾炎。在另外两种具有相似H-2不相容性的品系组合中[BALB/c注入BALB/c×BL10（BALB/c GvHD）以及BALB.D2注入BALB.D2×BL10（BALB.D2 GvHD）]，诱导GvHD会导致狼疮性肾炎但无全球性肾小球硬化。本研究调查了这三种品系组合中浸润肾脏的白细胞的特性及其在肾小球硬化发展过程中的作用。在患有DBA/2 GvHD的小鼠中，疾病诱导4周后肾小球CD11a阳性细胞显著增加。患有BALB/c或BALB.D2 GvHD的小鼠在任何时间点均未显示肾小球CD11a阳性细胞增加。在间质中，仅在患有DBA/2 GvHD的小鼠疾病诱导4周后观察到CD11a阳性细胞。在患有BALB.D2 GvHD的小鼠中，间质CD11a阳性细胞未发现增加。在患有BALB/c GvHD的小鼠中，从第4周起发现间质CD11a阳性细胞。对患有DBA/2 GvHD的小鼠肾小球CD11a阳性细胞进行的进一步免疫组织化学分析表明，这些细胞既不是多形核白细胞（PMN），也不是CD3阳性（T细胞）、B220阳性（B细胞）或F4/80阳性（巨噬细胞）。它们均为CD45阳性（白细胞）且MHC II类阳性。总之，我们在这个慢性狼疮性肾炎模型中表明，尚未确定身份的CD11a阳性白细胞向肾小球的流入与肾小球硬化的发展有关。
