Abstract:
: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), re-express 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.
journal_name
Bloodjournal_title
Bloodauthors
Waller EC,McKinney N,Hicks R,Carmichael AJ,Sissons JG,Wills MRdoi
10.1182/blood-2007-07-104604subject
Has Abstractpub_date
2007-12-15 00:00:00pages
4360-6issue
13eissn
0006-4971issn
1528-0020pii
blood-2007-07-104604journal_volume
110pub_type
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