Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide.
Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide.
复制标题
用小鼠甲状腺球蛋白和脂多糖诱导良好和不良响应者小鼠的自身免疫性。
DOI：
10.1084/jem.145.5.1250
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发表时间：
1977-05-01
影响因子：
15.3
通讯作者：
Kong, Y C
中科院分区：
文献类型：
--
作者：
Esquivel, P S;Rose, N R;Kong, Y C
可溶性小鼠甲状腺球蛋白（MTg）与细菌脂多糖（LPS）联合给药导致小鼠对MTg的自然耐受终止。自身免疫的程度与MTg的反应性相关，先前通过注射MTg的完全弗氏佐剂（CFA）显示依赖于H-2单倍型。在给予MTg与LPS或CFA的良好应答B10.BR（H-2k）小鼠中，观察到MTg的高抗体水平和甲状腺中广泛的单核细胞浸润。相比之下，给予MTg加LPS的同类低应答B10.D2（H-2d）小鼠与接受CFA中的MTg的小鼠相比显示低水平的MTg抗体，并且甲状腺的细胞浸润不显著。在任何情况下，自身免疫性发展无论是在良好或不良反应株给予MTg，LPS，或CFA沿着，虽然LPS是抗原在这两个同源株。由于已知对MTg的反应性的遗传差异是基于T细胞的，因此怀疑LPS处理的小鼠中T细胞的参与。通过使用无胸腺低应答（BALB/c）小鼠和胸腺切除、辐照和骨髓重建的B10.BR小鼠进一步确定了这一点。仅在杂合子（nu/+）小鼠和用胸腺和骨髓细胞重建的良好应答小鼠中检测到MTg抗体。此外，甲状腺中的显著细胞浸润仅发生在完全重建的良好应答小鼠中。因此，LPS对MTg应答性的佐剂作用需要T细胞。由于未修饰的MTg和LPS消除了对MTg的自身耐受性，因此可以排除对交叉反应性T细胞的需要。这些观察结果表明存在自身反应性T细胞。
The administration of soluble mouse thyroglobulin (MTg) in conjunction with bacterial lipopolysaccharide (LPS) led to the termination of natural tolerance to MTg in mice. The extent of autoimmunity correlated with responsiveness to MTg, previously shown by the injection of MTg in complete Freund's adjuvant (CFA) to be dependent upon the H-2 haplotype. In good responder B10.BR (H-2k) mice given MTg either with LPS or in CFA, high antibody levels to MTg and extensive mononuclear cell infiltration in the thyroid were observed. In contrast, congenic poor responder B10.D2 (H-2d) mice given MTg plus LPS showed low levels of antibody to MTg, compared to those receiving MTg in CFA, and insignificant cellular infiltration of the thyroid. In no instance did autoimmunity develop in either good or poor responder strain given MTg, LPS, or CFA along although LPS was antigenic in both of these congenic strains. Since the genetic difference in responsiveness to MTg is known to be T-cell based, the involvement of T cells in LPS-treated mice was suspected. This was further ascertained by the use of athymic poor responder (BALB/c) mice and thymectomized, irradiated, and bone marrow- reconstituted B10.BR mice. Antibodies to MTg were detected only in heterozygous (nu/+) mice and good responder mice reconstituted with both thymus and bone marrow cells. In addition, significant cellular infiltration in the thyroid occurred only in fully reconstituted good responder mice. Thus, the adjuvant effect of LPS on responsiveness to MTg required T cells. Since unmodified MTg and LPS abrogated selftolerance to MTg, the need for cross-reactive T cells could be excluded. These observations suggest the presence of self-reactive T cells.