Induction of Oral Tolerance in Splenocyte-Reconstituted SCID Mice

Hiroko Yoshida , Satoshi Hachimura , Kazuki Hirahara , Tatsuhiro Hisatsune , Ken-ichi Nishijima , Akio Shiraishi , Shuichi Kaminogawa
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引用次数: 18

Abstract

The participation of each lymphocyte compartment in the induction of oral tolerance for antibody response was investigated by means of a new cell-transfer experimental system, using severe combined immunodeficiency (SCID) mice. Various lymphocyte compartments from BALB/c mice were transferred into SCID mice and these mice were evaluated for oral tolerance induction. First, whole splenocytes from BALB/c mice were transferred into SCID mice and these mice were orally administered bovine αs1-casein. The specific antibody response in these mice after subsequent immunization with antigen was greatly reduced compared to controls which were not fed the antigen, and it was demonstrated that oral tolerance was induced in SCID mice bearing donor splenocytes. Oral tolerance was induced in SCID mice that were reconstituted with only T cells, revealing that B cells were not required for the induction of oral tolerance. Further, oral tolerance was induced in SCID mice reconstituted with CD8-depleted splenocytes but not in mice reconstituted with only CD8+T cells. These results demonstrate that oral tolerance could be induced in SCID mice bearing normal splenocytes and that interaction of CD4+T cells with antigen-presenting cells other than B cells are responsible for the induction of oral tolerance. Our experimental system may be useful for investigations with human lymphocytes.

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脾细胞重组SCID小鼠口服耐受的诱导
通过一种新的细胞转移实验系统,利用严重联合免疫缺陷(SCID)小鼠,研究了每个淋巴细胞室在诱导口服抗体耐受反应中的参与情况。将BALB/c小鼠的各种淋巴细胞区室转移到SCID小鼠中,并评估这些小鼠的口服耐受诱导。首先,将BALB/c小鼠的整个脾细胞转移到SCID小鼠中,并给这些小鼠口服牛α 51 -酪蛋白。这些小鼠在随后的抗原免疫后的特异性抗体反应与未喂食抗原的对照组相比大大降低,并且证明在携带供体脾细胞的SCID小鼠中诱导了口服耐受。在仅用T细胞重组的SCID小鼠中诱导口服耐受,表明B细胞不需要诱导口服耐受。此外,用CD8缺失的脾细胞重组的SCID小鼠可诱导口服耐受,而仅用CD8+T细胞重组的小鼠则不能。这些结果表明,具有正常脾细胞的SCID小鼠可以诱导口服耐受,并且CD4+T细胞与抗原呈递细胞(而不是B细胞)的相互作用是诱导口服耐受的原因。我们的实验系统可能对人类淋巴细胞的研究有用。
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