Differential costimulation through CD137 (4–1BB) restores proliferation of human virus-specific “effector memory” (CD28− CD45RAHI) CD8+ T cells
ECP Waller, N McKinney, R Hicks… - Blood, The Journal …, 2007 - ashpublications.org
ECP Waller, N McKinney, R Hicks, AJ Carmichael, JGP Sissons, MR Wills
Blood, The Journal of the American Society of Hematology, 2007•ashpublications.orgIn healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8+ T-
cell population is often dominated by CD28− CD45RAhi 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− CD45RAhi 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 …
cell population is often dominated by CD28− CD45RAhi 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− CD45RAhi 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 …
In healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8+ T-cell population is often dominated by CD28− CD45RAhi 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− CD45RAhi 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+ CD45ROhi cells or CD28− CD45ROhi 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− CD45RAhi CD8+ T cells and not CD80, CD86, or CD275 (ICOSL). Therefore, CD28− CD45RAhi CD8+ T cells were not terminally differentiated but required a specific costimulatory signal for proliferation.
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