Restoration of CD28 expression in CD28-CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production

被引:115
作者
Topp, MS
Riddell, SR
Akatsuka, Y
Jensen, MC
Blattman, JN
Greenberg, PD
机构
[1] Fred Hutchinson Canc Res Ctr, Program Immunol, Div Clin Res, Seattle, WA 98109 USA
[2] Univ Washington, Dept Med, Seattle, WA 98195 USA
[3] City Hope Natl Med Ctr, Div Pediat, Duarte, CA 90195 USA
[4] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
关键词
CD8+T cells; CD28; interleukin-2; costimulation; memory response;
D O I
10.1084/jem.20021288
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The control of many persistent viral infections by Ag-specific cytolytic CD8(+) T cells requires a concurrent virus-specific CD4(+) Th cell response. This reflects in part a requirement of activated effector CD8(+) T cells for paracrine IL-2 production as a growth and survival factor. In human CMV and HIV infection, the majority of differentiated virus-specific CD8(+) T cells notably lose the ability to produce IL-2 but also lose expression of CD28, a costimulatory molecule. Analysis of the fraction of memory CD8(+) T cells that continue to express CD28 revealed these cells retain the ability to produce IL-2. Therefore, we examined if IL-2 production by CD28(-) CD8(+) T cells could be restored by introduction of a constitutively expressed CD28 gene. Expression of CD28 in CD28(-) CD8(+) CMV- and HIV-specific CD8(+) T cells reconstituted the ability to produce IL-2, which could sustain an autocrine proliferative response after Ag recognition. These results suggest that the loss of CD28 expression during differentiation of memory/effector CD8(+) T cells represents a decisive step in establishing regulation of responding CD8(+) T cells, increasing the dependence on CD4(+) Th for proliferation after target recognition, and has implications for the treatment of viral disease with adoptively transferred CD8(+) T cells.
引用
收藏
页码:947 / 955
页数:9
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