Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease

被引:155
作者
Bustamante, Juan M. [1 ]
Bixby, Lisa M. [1 ,2 ]
Tarleton, Rick L. [1 ,2 ]
机构
[1] Univ Georgia, Coverdell Ctr, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA
[2] Univ Georgia, Coverdell Ctr, Dept Cellular Biol, Athens, GA 30602 USA
关键词
D O I
10.1038/nm1744
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this study, we document the development of stable, antigen-independent CD8(+) T cell memory after drug-induced cure of a chronic infection. By establishing a system for drug cure of chronic Trypanosoma cruzi infection, we present the first extensively documented case of total parasite clearance after drug treatment of this infection. Cure resulted in the emergence of a stable, parasite-specific CD8(+) T cell population with the characteristics of central memory cells, based upon expression of CD62L, CCR7, CD127, CD122, Bcl-2 and a reduced immediate in vivo CTL function. CD8(+) T cells from treated and cured mice also expanded more rapidly and provided greater protection following challenge than those from chronically infected mice. These results show that complete pathogen clearance results in stable, antigen-independent and protective T cell memory, despite the potentially exhausting effects of prior long-term exposure to antigen in this chronic infection.
引用
收藏
页码:542 / 550
页数:9
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