Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection

被引:163
作者
Vezys, Vaiva
Masopust, David
Kemball, Christopher C.
Barber, Daniel L.
O'Mara, Leigh A.
Larsen, Christian P.
Pearson, Thomas C.
Ahmed, Rafi
Lukacher, Aron E. [1 ]
机构
[1] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[4] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA
关键词
D O I
10.1084/jem.20060995
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Numerous microbes establish persistent infections, accompanied by antigen-specific CD8 T cell activation. Pathogen-specific T cells in chronically infected hosts are often phenotypically and functionally variable, as well as distinct from T cells responding to nonpersistent infections; this phenotypic heterogeneity has been attributed to an ongoing reencounter with antigen. Paradoxically, maintenance of memory CD8 T cells to acutely resolved infections is antigen independent, whereas there is a dependence on antigen for T cell survival in chronically infected hosts. Using two chronic viral infections, we demonstrate that new naive antigen-specific CD8 T cells are primed after the acute phase of infection. These newly recruited T cells are phenotypically distinct from those primed earlier. Long-lived antiviral CD8 T cells are defective in self-renewal, and lack of thymic output results in the decline of virus-specific CD8 T cells, indicating that newly generated T cells preserve antiviral CD8 T cell populations during chronic infection. These findings reveal a novel role for antigen in maintaining virus-specific CD8 T cells during persistent infection and provide insight toward understanding T cell differentiation in chronic infection.
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收藏
页码:2263 / 2269
页数:7
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