Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections.
The viruses HIV-1, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and hepatitis C virus (HCV) are characterized by the establishment of lifelong infection in the human host, where their replication is thought to be tightly controlled by virus-specific CD8+ T cells. Here we present detailed studies of the differentiation phenotype of these cells, which can be separated into three distinct subsets based on expression of the costimulatory receptors CD28 and CD27. Whereas CD8+ T cells specific for HIV, EBV and HCV exhibit similar characteristics during primary infection, there are significant enrichments at different stages of cellular differentiation in the chronic phase of persistent infection according to the viral specificity, which suggests that distinct memory T-cell populations are established in different virus infections. These findings challenge the current definitions of memory and effector subsets in humans, and suggest that ascribing effector and memory functions to subsets with different differentiation phenotypes is no longer appropriate.
Appay
Victor
V
MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK. vappay@gwmail.jr2.ox.ac.uk
Dunbar
P Rod
PR
Callan
Margaret
M
Klenerman
Paul
P
Gillespie
Geraldine M A
GM
Papagno
Laura
L
Ogg
Graham S
GS
King
Abigail
A
Lechner
Franziska
F
Spina
Celsa A
CA
Little
Susan
S
Havlir
Diane V
DV
Richman
Douglas D
DD
Gruener
Norbert
N
Pape
Gerd
G
Waters
Anele
A
Easterbrook
Philippa
P
Salio
Mariolina
M
Cerundolo
Vincenzo
V
McMichael
Andrew J
AJ
Rowland-Jones
Sarah L
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology; D003603:Cytotoxins / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D015497:HIV-1; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology* / Q000473:pathology
C515370:CCR7 protein, human; D018106:CD28 Antigens; D003603:Cytotoxins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens