title: Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans.
abstract: Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-gamma-producing effector-memory and proliferative memory T cells were compared in 79 vaccinees 13-25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-gamma-producing effector-memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-gamma-producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector-memory T cells. Programmed revaccination boosted both IFN-gamma and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector-memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.
authors.affiliation: Laboratoire d'Immunologie Cellulaire, INSERM U543, Paris, France.
authors.forename: Behazine
authors.initials: B
authors.lastname: Combadiere
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boissonnas
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lefranc
authors.forename: Assia
authors.initials: A
authors.lastname: Samri
authors.forename: François
authors.initials: F
authors.lastname: Bricaire
authors.forename: Patrice
authors.initials: P
authors.lastname: Debre
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012900:Smallpox Vaccine / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D012900:Smallpox Vaccine; D007371:Interferon-gamma