Pathogenesis of spontaneous hepatitis in LEC rats with combined immunodeficiency

本文对自发性肝炎的LEC大鼠进行了免疫病理学研究，并与非肝炎莱亚大鼠进行了比较。6周龄LEC大鼠脾脏和胸腺湿重明显低于同龄莱亚大鼠。4周龄后LEC大鼠血清IgG水平仍明显低于正常对照组。空斑法检测抗SRBC IgG抗体的形成也受到明显抑制。莱亚与LEC大鼠杂交后代的遗传学研究表明，肝炎的发生与IgG水平的降低密切相关：IgG水平相对较高的F_1代未发现肝炎病例，而IgG水平较低的F_2代和回交代则有较多的肝炎病例。LEC大鼠脾细胞对PHA和ConA的增殖反应明显低于莱亚大鼠，腹腔巨噬细胞对肿瘤细胞的抑制作用高于莱亚大鼠，但两种品系大鼠的NK活性无差异。根据这些结果，推测自发性肝炎发展的LEC大鼠具有T和B细胞缺陷（联合免疫缺陷），并且巨噬细胞和NK细胞活性的增加与肝炎发展的原因有关。

We investigated LEC rats which spontaneously develop hepatitis to findout the cause immunopathologically, in comparison with non hepatitis LEA rats.Wet weight of spleen and thymus of 6-week old LEC rats was significantly lighter then that of LEA rat of the same age.Serum IgG level in LEC rats remained markedly low after the age of 4 weeks, and IgG antibody form ation to SRBC as detected by plaque assay was also significantly suppressed. Furthermore, genetic studies of crossing hybrids of LEA and LEC rats revealed that there was a close correlation between development of hepatitis and lower levels of IgG: no hepatitis case was found in F_1 group which had relatively high IgG levels, but many in F_2 and backcross groups which had lower IgG levels. On the other hand, IgG and IgM antibody formation was suppressed, though serum IgM level was normal or rather increased.Blastgenic response of spleen cells to PHA and Con A was much more suppressed in LEC rats than in LEA rats.Cytostatic activity of intraperitoneal macrophage against tumor cells was more evident inLEC rats than in LEA rats, but there was no difference inNK activity between the two rat strains. From these results, it is speculated that spontaneously hepatitisdeveloping LEC rats possess T and B cell deficiency (combined immunodeficiency) and that the increase of macrophage and NK cell activitiesare linked to the cause of developing hepatitis.