Cutting edge:: Contact-mediated suppression by CD4+-CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism

Cutting edge:: Contact-mediated suppression by CD4+-CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism
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DOI:
10.4049/jimmunol.174.4.1783
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发表时间:
2005-02-15
影响因子:
4.4
通讯作者:
Noelle, RJ
Noelle, RJ
中科院分区:
医学2区
文献类型:
--
作者:
Gondek, DC;Lu, LF;Noelle, RJ

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CD 4(+)CD 25(+)调节性T细胞(T(reg))是有效的免疫抑制细胞,在外周耐受的调节中起关键作用。在这份报告中,我们确定颗粒酶B(GZ-B)的关键组成部分之一的T-g介导的抑制。调节活性的诱导与GZ-B表达的上调相关。来自GZ-B-/-小鼠的T1与来自W/T小鼠的T-reg一样有效地抑制的能力降低,证明了GZ-B在T-reg的接触介导的抑制中的功能参与。GZ-B介导的抑制是独立的,因为T-reg对穿孔素(-/-)和WT的抑制是不可区分的。此外,T-reg介导的抑制似乎部分通过诱导CD 4(+)CD 25(-)效应细胞的凋亡来介导。总之,GZ-B是CD 4(+)CD 25(+)T-reg诱导细胞接触介导的抑制的关键机制之一。
CD4(+) CD25(+) regulatory T cells (T (reg)) are potent immunosuppressive cells that are pivotal in the regulation of peripheral tolerance. In this report, we identify granzyme B (GZ-B) as one of the key components of T-g-mediated suppression. Induction of regulatory activity is correlated with the up-regulation of GZ-B expression. Proof of a functional involvement of GZ-B in contact-mediated suppression by T-reg is shown by the reduced ability of T, from GZ-B-/- mice to suppress as efficiently as T-reg from W/T mice. GZ-B-mediated suppression is perform independent, because suppression by T-reg from perforin(-/-) and WT is indistinguishable. Additionally, suppression mediated by T-reg appears to be mediated, inpart, by the induction of apoptosis in the CD4(+) CD25(-) effector cell. In summary, GZ-B is one of the key mechanisms through which CD4(+) CD25(+) T-reg induce cell contact-mediated suppression.