Differential costimulation through CD137 (4-1BB) restores proliferation of human virus-specific "effector memory" (CD28- CD45RAHI) CD8+ T cells

被引:69
作者
Waller, Edward C. P. [1 ]
McKinney, Nicola [1 ]
Hicks, Ray [1 ]
Carmichael, Andrew J. [1 ]
Sissons, J. G. Patrick [1 ]
Wills, Mark R. [1 ]
机构
[1] Univ Cambridge, Dept Med, Sch Clin, Cambridge CB2 2QQ, England
基金
英国医学研究理事会;
关键词
D O I
10.1182/blood-2007-07-104604
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8(+) T-cell population is often dominated by CD28(-) CD45RA(hi) cells that exhibit direct ex vivo cytotoxicity but whose capacity for proliferation and generation of further memory cells has been questioned. We show that when highly purified CD28(-) CD45RA(hi) CD8(+) T cells are stimulated with viral peptide presented by autologous monocytes, the virus-specific T cells show early up-regulation of CD137 (4-1BB) and CD278 (ICOS), reexpress CD28, and proliferate with similarly high cloning efficiency in limiting dilution analysis as CD28(+) CD45RO(hi) cells or CD28(-) CD45RO(hi) cells. Using peptide-pulsed autologous fibroblasts transfected with individual costimulatory ligands as antigen presenting cells, we showed CD137L to be a key costimulatory ligand for proliferation of CD28(-) CD45RA(hi) CD8(+) T cells and not CD80, CD86, or CD275 (ICOSL). Therefore, CD28(-) CD45RA(hi) CD8+ T cells were not terminally differentiated but required a specific costimulatory signal for proliferation.
引用
收藏
页码:4360 / 4366
页数:7
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