Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection

Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection
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DOI:
10.1016/s1074-7613(04)00054-8
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发表时间:
2004-03-01
期刊:
影响因子:
32.4
通讯作者:
Hasenkrug, KJ
Hasenkrug, KJ
中科院分区:
医学1区
文献类型:
--
作者:
Dittmer, U;He, H;Hasenkrug, KJ

文献摘要

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The establishment of viral persistence generally requires evasion of the host CD8(+) T cell response. Here we describe a form of evasion wherein the CD8(+) T cells are fully capable of recognizing their cognate antigen but their effector functions are suppressed by regulatory T cells. Virus-specific CD8(+) T cells adoptively transferred into mice persistently infected with Friend virus proliferated and appeared activated, but failed to produce IFNgamma or reduce virus loads. Cotransfer experiments revealed that a subpopulation of CD4(+) T cells from persistently infected mice suppressed IFNgamma production by the CD8(+) T cells. Treatment of persistently infected mice with anti-GITR antibody to ameliorate suppression by regulatory T cells significantly improved IFNgamma production by transferred CD8(+) T cells and allowed a significant reduction in viral loads. The results indicate that CD4(+) regulatory T cells contribute to viral persistence and demonstrate an immunotherapy for treating chronic retroviral infections.