CD18 is required for optimal development and function of CD4+ CD25+ T regulatory cells
CD18 is required for optimal development and function of CD4+ CD25+ T regulatory cells
复制标题
DOI：
10.4049/jimmunol.175.12.7889
复制
发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Abraham, C
中科院分区：
文献类型：
--
作者：
Marski, M;Kandula, S;Abraham, C
CD4(+)CD25(+) T调节（Treg）细胞在体内抑制免疫病理和自身免疫性疾病。CD4(+)CD25(+) Treg细胞体外抑制常规T细胞的能力依赖于细胞间接触；然而，介导这种细胞接触的细胞表面分子尚未被确定。LFA-1 （CD11a/CD18）是一种粘附分子，在T细胞介导的细胞接触和T细胞活化中起着既定的作用。尽管LFA-1在小鼠CD4(+)CD25(+) Treg细胞中高水平表达，但LFA-1在这些细胞中的作用尚未明确。我们假设LYA-1可能在小鼠CD4(+)CD25(+) Treg功能中发挥作用。为了评估这一点，我们分析了lfa -1缺陷（CD.18(-/-)） CD4(+)CD25(+) t细胞。我们发现CD18（-/-）小鼠表现出自身免疫的倾向。缺乏CD18导致CD4(+)CD25(+) T细胞数量减少，并影响这些细胞的胸腺和外周发育。lfa -1缺陷的CD4(+)CD25(+) T细胞在体外介导抑制和介导由CD4(+)CD25(-) T细胞转移到淋巴细胞减少宿主诱导的结肠炎的保护方面存在缺陷。因此，我们确定了CD18在最佳CD4(+)CD25(+) Treg发育和功能中的关键作用。
CD4(+)CD25(+) T regulatory (Treg) cells inhibit immunopathology and autoimmune disease in vivo. CD4(+)CD25(+) Treg cells' capacity to inhibit conventional T cells in vitro is dependent upon cell-cell contact; however, the cell surface molecules mediating this cell:cell contact have not yet been identified. LFA-1 (CD11a/CD18) is an adhesion molecule that plays an established role in T cell-mediated cell contact and in T cell activation. Although expressed at high levels on murine CD4(+)CD25(+) Treg cells, the role of LFA-1 in these cells has not been defined previously. We hypothesized that LYA-1 may play a role in murine CD4(+)CD25(+) Treg function. To evaluate this, we analyzed LFA-1-deficient (CD.18(-/-)) CD4(+)CD25(+) Tcells. We show that CD18(-/-) mice demonstrate a propensity to autoinumunity. Absence of CD18 led to diminished CD4(+)CD25(+) T cell numbers and affected both thymic and peripheral development of these cells. LFA-1-deficient CD4(+) CD25(+) T cells were deficient in mediating suppression in vitro and in mediating protection from colitis induced by the transfer of CD4(+)CD25(-) T cells into lymphopenic hosts. Therefore, we define a crucial role for CD18 in optimal CD4(+)CD25(+) Treg development and function.