Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro
Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro
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DOI：
10.4049/jimmunol.174.7.4090
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Ishida, Y
中科院分区：
文献类型：
--
作者：
Shimizu, J;Iida, R;Ishida, Y
CD 4（+）CD 25（+）T细胞具有免疫调节和抑制功能，并负责抑制自身反应细胞和维持自身耐受。除了CD 4（+）CD 25（+）T细胞外，有一些证据表明一部分CD 4（+）CD 25（-）T细胞在体外或体内表现出抑制活性。我们已经用老年小鼠证明，衰老不仅导致建立CD 4（+）CD 25（-）T细胞应答的能力下降，而且同时使衰老的CD 4（+）CD 25（-）T细胞具有抑制性。在这项研究中，我们报告了两个新建立的单克隆抗体，可以消除老年CD 4（+）CD 25（-）T细胞的抑制功能。这些单克隆抗体识别相同的蛋白质，跨膜磷酸酶CD 45。老化的CD 4（+）CD 25（-）T细胞上的CD 45交联是破坏其抑制活性所必需的。令人惊讶的是，这些mAb还在体外消除了CD 4（+）CD 25（+）T细胞的抑制作用。我们的研究结果表明，CD 45作为负调节因子的一种意想不到的功能，可以中和老年CD 4（+）CD 25（-）和年轻CD 4（+）CD 25（+）T细胞的抑制活性。
CD4(+)CD25(+) T cells have immunoregulatory and suppressive functions and are responsible for suppressing self-reactive cells and maintaining self-tolerance. In addition to CD4(+)CD25(+) T cells, there is some evidence that a fraction of CD4(+)CD25(-) T cells exhibit suppressive activity in vitro or in vivo. We have shown, using aged mice, that aging not only leads to a decline in the ability to mount CD4(+)CD25(-) T cell responses, but, at the same time, renders aged CD4(+)CD25(-) T cells suppressive. In this study we report two newly established mAbs that could abrogate the suppressive function of aged CD4(+)CD25(-) T cells. These mAbs recognized the same protein, the transmembrane phosphatase CD45. Cross-linking of CD45 on aged CD4(+)CD25(-) T cells was required for the disruption of their suppressive activity. Surprisingly, these mAbs also abrogated the suppressive action of CD4(+)CD25(+) T cells in vitro. Our results demonstrate an unexpected function of CD45 as a negative regulator neutralizing the suppressive activity of aged CD4(+)CD25(-) and young CD4(+)CD25(+) T cells.