Regulation of murine chronic colitis by CD4+CD25- programmed death-1+ T cells
Regulation of murine chronic colitis by CD4+CD25- programmed death-1+ T cells
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DOI：
10.1002/eji.200425109
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Watanabe, M
中科院分区：
文献类型：
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作者：
Totsuka, T;Kanai, T;Watanabe, M
自然产生的CD 4（+）CD 25（+）调节性T（T-R）细胞参与维持自身耐受和预防自身免疫性疾病。然而，越来越多的证据表明，一部分外周血CD 4（+）CD 25（-）T细胞也具有调节活性。程序性死亡-1（PD-1）是CD 28/CTLA-4家族的新成员，参与外周自身耐受的维持。在此，我们在未处理小鼠的脾脏中鉴定了CD 4（+）CD 25（-）PD-1（+）T细胞亚群，其组成性表达CTLA-4和FoxP 3，并且在体外对抗CD 3抗体刺激的应答中低增殖。然而，与CD 4（+）CD 25（+）TR细胞不同，CD 4（+）CD 25（-）PD-1（+）T细胞响应于抗CD 3和抗CD 28 mAb刺激而独特地产生大量IL-4和IL-10。CD 4（+）CD 25（-）PD-1（+）T细胞在体外对抗CD 3抗体刺激的CD 4（+）CD 25（-）PD-1（-）T细胞的增殖具有抑制作用，抗CTLA-4单抗可部分抑制其增殖，但抗IL-10或抗PD-1单抗不能抑制其增殖。值得注意的是，CD 4（+）CD 25（-）PD-1（+）T细胞以CTLA-4依赖性方式抑制由CD 4（+）CD 45 RB（高）T细胞过继转移到C.B17-scid/scid小鼠中诱导的结肠炎的发展，尽管程度低于CD 4（+）CD 25（+）TR细胞。这些结果表明，CD 4（+）CD 25（-）PD-1（+）T细胞含有大量的TR细胞参与维持外周耐受。
Naturally arising CD4(+)CD25(+) regulatory T (T-R) cells are engaged in the maintenance of self tolerance and prevention of autoimmune diseases. However, accumulating evidence suggests that a fraction of peripheral CD4(+)CD25(-) T cells also possesses regulatory activity. Programmed death-1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in the maintenance of peripheral self tolerance. Here, we identified a subpopulation of CD4(+)CD25(-)PD-1(+) T cells in the spleen of naive mice that constitutively expressed CTLA-4 and FoxP3 and was hypoproliferative in response to anti-CD3 antibody stimulation in vitro. However, the CD4(+)CD25(-)PD-1(+) T cells uniquely produced large amounts of IL-4 and IL-10 in response to anti-CD3 and anti-CD28 mAb stimulation, unlike the CD4(+)CD25(+) TR cells. The CD4(+)CD25(-)PD-1(+) T cells exhibited a suppressor activity against the proliferation of anti-CD3 antibody-stimulated CD4(+)CD25(-)PD-1(-) T cells in vitro, which was partially abrogated by anti-CTLA-4 mAb, but not by anti-IL-10 or anti-PD-1 mAb. Remarkably, the CD4(+)CD25(-)PD-1(+) T cells inhibited the development of colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells into C.B17-scid/scid mice, albeit to a lesser extent than CD4(+)CD25(+) TR Cells, in a CTLA-4-dependent manner. These results indicate that the CD4(+)CD25(-)PD-1(+) T cells contain substantial amounts of TR cells that are involved in the maintenance of peripheral tolerance.