Myelin proteolipid protein-specific CD4+ CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis
Myelin proteolipid protein-specific CD4+ CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis
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DOI：
10.1073/pnas.0404444101
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发表时间：
2004-10-26
影响因子：
11.1
通讯作者：
Kuchroo, VK
中科院分区：
文献类型：
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作者：
Reddy, J;Illes, Z;Kuchroo, VK
SJL小鼠对髓鞘蛋白脂质蛋白（PLP）肽139-151诱导的实验性自身免疫性脑脊髓炎（EAE）高度易感，而H-2同源B10.S小鼠具有抗性。免疫优势和对EAE的易感性与SA小鼠幼稚库中PLP 139-151特异性T细胞的高前体频率相关。为了理解B10.S小鼠中EAE抗性的机制，我们通过使用IA（s）/PLP 139 - 151四聚体测定两种品系中PLP 139 - 151反应性T细胞的前体频率。SJL和B10.S小鼠在幼稚外周库中具有相似的四聚体反应性T细胞频率。然而，在SJL小鼠中，大多数PLP 139-151四聚体阳性细胞在CD 4（+）CD 25（-）群体中，而在B10.S小鼠的CD 4（+）CD 25（+）群体中有更多的四聚体阳性细胞。体内CD 4（+）CD 25（+）细胞的消耗促进了PLP 139-151反应性细胞的扩增，并在EAE抗性B10.S小鼠中产生T辅助细胞1细胞因子。此外，免疫前抗CD 25 Ab治疗导致这些其他抗性小鼠中的EAE诱导。这些数据表明自身抗原特异性CD 4（+）CD 25（+）细胞在自身免疫的遗传抗性中起重要作用。
SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139-151-specific T cells in the naive repertoire of SA mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139-151-reactive T cells in both strains by using IA(s)/PLP 139-151 tetramers. SJL and B10.S mice had similar frequencies of tetra mer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the majority of PLP 139-151 tetramer-positive cells were in the CD4(+)CD25(-) population, whereas there were more tetra mer-positive cells in the CD4(+)CD25(+) population of B10.S mice. Depletion of CD4(+)CD25(+) cells in vivo facilitated the expansion of PLP 139-151-reactive cells with production of T helper 1 cytokines in EAE-resistant B10.S mice. Furthermore, anti-CD25 Ab treatment before immunization resulted in EAE induction in these otherwise resistant mice. These data indicate an important role for autoantigen-specific CD4(+)CD25(+) cells in genetic resistance to autoimmunity.