González M, Schurmans S, Ramos A, Merino R, Lambert P H, Merino J
S. Inmunología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Eur J Immunol. 1995 Jun;25(6):1760-4. doi: 10.1002/eji.1830250641.
Spleen cells from F1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomerulonephritis. Previous reports indicated that the depletion of F1 donor T cells, shortly prior the injection into parental mice, does not interfere with any of these events. Here, we have explored whether the continuous absence of T cells in F1 mice influences the ability of their spleen cells to induce neonatal tolerance to alloantigens and the associated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c x C57BL/6) F1 hybrid (CB6F1) nu/nu mice or from euthymic CB6F1 mice depleted from birth of CD4+ T cells, but not of CD8+ T cells, are unable to induce neonatal tolerance to alloantigens and autoimmune manifestations. By contrast, the partial reconstitution of T cells in CB6F1 nu/nu mice, after the neonatal graft of a syngeneic thymus, restored the capacity of spleen cells from these mice to induce tolerance and autoimmunity when injected into newborn BALB/c mice. These results demonstrate that the functional defect of spleen cells from athymic CB6F1 nu/nu mice to induce neonatal tolerance to alloantigens is directly related to the long-term absence of mature CD4+ T cells. Interestingly, a new increase in the titers of anti-DNA Ab was observed when spleen cells from athymic CB6F1 nu/nu mice were injected into adult BALB/c mice that had been tolerized at birth with normal CB6F1 spleen cells. This finding indicates that B cells from CB6F1 nu/nu mice recover their capacity to interact with alloreactive Th2 cells when they are placed into mice having functional CD4+ T cells. These data indicate that the continuous absence of CD4+ T cells causes a reversible functional defect in F1 spleen cells that determines their inability to induce neonatal tolerance and autoimmunity.
将F1杂交小鼠的脾细胞注射到新生的亲代小鼠中，可诱导出对相应同种异体抗原的溶细胞无反应状态。然而，这些小鼠会发展出一种短暂的自身免疫综合征，其特征是产生多种自身抗体和肾小球肾炎。先前的报告表明，在将F1供体T细胞注射到亲代小鼠之前不久对其进行清除，并不会干扰这些事件中的任何一个。在此，我们探究了F1小鼠中T细胞的持续缺失是否会影响其脾细胞诱导新生小鼠对同种异体抗原产生耐受性以及相关自身免疫表现的能力。我们的结果显示，来自无胸腺（BALB/c×C57BL/6）F1杂交（CB6F1）nu/nu小鼠的脾细胞，或来自出生时就清除了CD4⁺T细胞而非CD8⁺T细胞的有胸腺CB6F1小鼠的脾细胞，无法诱导新生小鼠对同种异体抗原产生耐受性以及出现自身免疫表现。相比之下，在新生的CB6F1 nu/nu小鼠移植了同基因胸腺后，T细胞的部分重建恢复了这些小鼠脾细胞在注射到新生BALB/c小鼠体内时诱导耐受性和自身免疫的能力。这些结果表明，无胸腺的CB6F1 nu/nu小鼠的脾细胞诱导新生小鼠对同种异体抗原产生耐受性的功能缺陷与成熟CD4⁺T细胞的长期缺失直接相关。有趣的是，当将来自无胸腺CB6F1 nu/nu小鼠的脾细胞注射到出生时已用正常CB6F1脾细胞诱导耐受的成年BALB/c小鼠体内时，观察到抗DNA抗体滴度有新的升高。这一发现表明，当CB6F1 nu/nu小鼠的B细胞置于具有功能性CD4⁺T细胞的小鼠体内时，它们恢复了与同种异体反应性Th2细胞相互作用的能力。这些数据表明，CD4⁺T细胞的持续缺失导致F1脾细胞出现可逆的功能缺陷，这决定了它们无法诱导新生小鼠产生耐受性和自身免疫。
