Differential costimulation through CD137 (4-1BB) restores proliferation of human virus-specific "effector memory" (CD28(-) CD45RA(HI)) CD8(+) T cells.

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

Blood

journal_title

Blood

authors

Waller EC,McKinney N,Hicks R,Carmichael AJ,Sissons JG,Wills MR

doi

10.1182/blood-2007-07-104604

subject

Has Abstract

pub_date

2007-12-15 00:00:00

pages

4360-6

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2007-07-104604

journal_volume

110

pub_type

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