Journal
BLOOD
Volume 110, Issue 13, Pages 4360-4366Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-07-104604
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Funding
- Medical Research Council [G0701279, G9800943, G9202171] Funding Source: Medline
- Medical Research Council [G9202171, G9800943] Funding Source: researchfish
- MRC [G9202171, G9800943] Funding Source: UKRI
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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.
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