Induction of oral tolerization in CD86 deficient mice:: A role for CD86 and B cells in the up-regulation of TGF-β
Induction of oral tolerization in CD86 deficient mice:: A role for CD86 and B cells in the up-regulation of TGF-β
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DOI：
10.1016/j.jaut.2005.10.003
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发表时间：
2006-03-01
影响因子：
12.8
通讯作者：
Weiner, HL
中科院分区：
文献类型：
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作者：
Gonnella, PA;Chen, YH;Weiner, HL
饲喂髓鞘少突胶质细胞糖蛋白（MOG）后免疫可诱导口服耐受，实验性自身免疫性脑脊髓炎（EAE）的改善证明了这一点。口服耐受性的特点是抑制Th1反应，上调Th2反应和tgf - β。为了确定参与细胞因子介导抑制的共刺激分子和细胞类型，我们研究了野生型小鼠和CD86（CD86(-/-)）或B细胞（mu MT）缺失的小鼠。在CD86（-/-）小鼠中发现口服耐受性，证明了疾病严重程度的改善，增殖反应和ifn - γ产生的降低以及IL-4的增加。tgf - β在CD86（-/-）或mu MT小鼠中未上调，但在野生型小鼠中升高。对饲喂不同髓鞘抗原（MOG和MBP）的小鼠（C57BL/6和PLJ x SJL F1）的肠道相关淋巴组织（GALT）进行分析发现，两株野生型小鼠的tgf - β在免疫后3 d均升高，并随着时间的推移进一步升高。相比之下，CD86（-/-）或mu MT小鼠的GALT未发现tgf - β上调。这些结果表明，CD86不是口服耐受所必需的，CD86和B细胞对口服抗原后tgf - β的上调都很重要。(c) 2005 Elsevier Ltd版权所有。
Feeding myelin oligodendrocyte glycoprotein (MOG) followed by immunization results in induction of oral tolerance evidenced by the amelioration of experimental autoimmune encephalomyelitis (EAE). Oral tolerization is characterized by the suppression of Th1 responses and up-regulation of Th2 responses and TGF-beta. To identify the costimulatory molecules and cell types involved in cytokine-mediated suppression we examined wild type mice and mice deficient for either CD86 (CD86(-/-)) or B cells (mu MT). Oral tolerance was found in CD86(-/-) mice evidenced by amelioration of disease severity, decreased proliferative responses and IFN-gamma production and increased IL-4. TGF-beta was not up-regulated in CD86(-/-) or mu MT mice but was increased in wild type mice. Analysis of the gut associated lymphoid tissue (GALT) of different mouse strains (C57BL/6 and PLJ x SJL F1) fed distinct myelin antigens (MOG and myelin basic protein, MBP) showed that TGF-beta was increased in wild type mice of both strains by 3 days post-immunization and further increased with time. In contrast, no up-regulation of TGF-beta was found in the GALT of CD86(-/-) or mu MT mice. These results demonstrate that CD86 is not required for oral tolerization and that both CD86 and B cells are important for the up-regulation of TGF-beta following oral antigen. (c) 2005 Elsevier Ltd. All rights reserved.