Immunosenescent colitogenic CD4+ T cells convert to regulatory cells and suppress colitis
Immunosenescent colitogenic CD4+ T cells convert to regulatory cells and suppress colitis
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DOI：
10.1002/eji.200737914
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发表时间：
2008-05-01
影响因子：
5.4
通讯作者：
Watanabe, Mamoru
中科院分区：
文献类型：
--
作者：
Totsuka, Teruji;Kanai, Takanori;Watanabe, Mamoru
炎症性肠病通过致结肠炎 CD4(+) 细胞的扩增而稳步进展。然而，仍不清楚致结肠炎CD4(+)细胞是像记忆细胞一样长寿，还是像效应细胞一样耗尽。为了评估致结肠炎固有层（LP）CD4（+）细胞的寿命，我们将结肠炎CD4（+）CD45RB（高）细胞转移的SCID小鼠中的LP CD4（+）细胞顺序转移到新的SCID小鼠中。虽然移植了结肠炎LP CD4(+)细胞的SCID小鼠至少在第六次移植之前稳定地发展为结肠炎，但随着移植次数的增加，发展为结肠炎的间隔逐渐延长。第七次转移后结肠炎的发病率逐渐下降。此外，与第一次转移后恢复的结肠炎LP CD4(+)细胞相比，来自转移七次以上的小鼠的非结肠炎LP CD4(+)细胞表达显着更高水平的PD-1，并产生显着较低量的IFN-γ、TNF-α和IL-17。最值得注意的是，我们发现多次转移后恢复的非结肠炎LP CD4(+)细胞的再转移可防止与CD4(+)CD45RB(high)细胞共转移的SCID小鼠发生结肠炎。因此，致结肠炎LP CD4(+)细胞可能随着时间的推移而耗尽，变得无功能，转化为调节细胞，并最终在免疫衰老过程中抑制结肠炎。
Inflammatory bowel diseases progress steadily by the expansion of colitogenic CD4(+) cells. However, it remains unknown whether colitogenic CD4(+) cells are long-living like memory cells or exhausted like effector cells. To assess the longevity of colitogenic lamina propria (LP) CD4(+) cells, we performed sequential transfers of LP CD4(+) cells from colitic CD4(+)CD45RB(high) cell-transferred SCID mice into new SCID mice. Although SCID mice transferred with colitic LP CD4(+) cells stably developed colitis until at least the sixth transfer, the interval to the development of colitis gradually lengthened as the number of transfers increased. The incidence of colitis gradually decreased after the seventh transfer. Furthermore, non-colitic LP CD4(+) cells from mice transferred over seven times expressed significantly higher levels of PD-1 and produced significantly lower amounts of IFN-gamma, TNF-alpha, and IL-17 than colitic LP CD4(+) cells recovered after the first transfer. Most notably, we found that re-transfer of non-colitic LP CD4(+) cells recovered after multiple transfers prevented the development of colitis in SCID mice co-transferred with CD4(+)CD45RB(high) cells. Thus, colitogenic LP CD4(+) cells may be exhausted over time, become non-functional, convert to regulatory cells, and finally suppress colitis in the process of immunosenescence.