Proliferation requirements of cytomegalovirus-specific, effector-type human CD8+ T cells.
Two prototypic types of virus-specific CD8(+) T cells can be found in latently infected individuals: CD45R0(+)CD27(+)CCR7(-) effector-memory, and CD45RA(+)CD27(-)CCR7(-) effector-type cells. It has recently been implied that CD45RA(+)CD27(-)CCR7(-) T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA(+)CD27(-)CCR7(-) T cells with their cognate peptide in concert with either CD4(+) help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion. Concurrently, these stimulated effector T cells change cell surface phenotype from CD45RA to CD45R0 and regain CCR7, while effector functions are maintained. Our data imply that CD45RA(+)CD27(-)CCR7(-) effector-type T cells contribute to immunity not only by direct execution of effector functions, but also by yielding progeny in situations of viral reinfection or reactivation.
van Leeuwen
Ester M
EM
Department of Internal Medicine, Divisions of Nephrology and Clinical Immunology and Rheumatology, Academic Medical Center, Meibergsreef 9, 1105 AZ Amsterdam, The Netherlands.
Gamadia
Laila E
LE
Baars
Paul A
PA
Remmerswaal
Ester B
EB
ten Berge
Ineke J
IJ
van Lier
René A
RA
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000502:physiology; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D014373:Tuberculin / Q000502:physiology; D014763:Viral Matrix Proteins / Q000502:physiology; D000098546:Interleukin-21
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D019409:Interleukin-15; D007376:Interleukin-2; D007378:Interleukins; D010750:Phosphoproteins; D014373:Tuberculin; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D000098546:Interleukin-21