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-γ–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-γ–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-γ–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-γ 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.
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7 June 2004
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June 07 2004
Distinct Time Effects of Vaccination on Long-Term Proliferative and IFN-γ–producing T Cell Memory to Smallpox in Humans
Behazine Combadiere,
Behazine Combadiere
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
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Alexandre Boissonnas,
Alexandre Boissonnas
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
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Evelyne Lefranc,
Evelyne Lefranc
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
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Assia Samri,
Assia Samri
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
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François Bricaire,
François Bricaire
2Service de Maladies Infectieuses, Hôpital Pitié-Salpétrière, Université Pierre et Marie Curie, 75013 Paris, France
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Patrice Debre,
Patrice Debre
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
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Brigitte Autran
Brigitte Autran
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
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Behazine Combadiere
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
Alexandre Boissonnas
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
Guislaine Carcelain
Evelyne Lefranc
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
Assia Samri
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
François Bricaire
2Service de Maladies Infectieuses, Hôpital Pitié-Salpétrière, Université Pierre et Marie Curie, 75013 Paris, France
Patrice Debre
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
Brigitte Autran
1 Laboratoire d'Immunologie Cellulaire, INSERM U543,
Correspondence should be addressed to Brigitte Autran, Laboratoire d'Immunologie Cellulaire, Hôpital Pitié-Salpétrière, 83 Bd de l'Hôpital, 75013 Paris, France. Phone: 33-1-42-177481; Fax: 33-1-42-177490; email: [email protected]
B. Combadiere and A. Boissonnas contributed equally to this work.
Abbreviations used in this paper: BCG, Bacille de Calmette et Guérin; BrdU, bromodeoxyuridine; SFC, spot-forming cell.
Received:
December 03 2003
Accepted:
April 28 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2004
J Exp Med (2004) 199 (11): 1585–1593.
Article history
Received:
December 03 2003
Accepted:
April 28 2004
Citation
Behazine Combadiere, Alexandre Boissonnas, Guislaine Carcelain, Evelyne Lefranc, Assia Samri, François Bricaire, Patrice Debre, Brigitte Autran; Distinct Time Effects of Vaccination on Long-Term Proliferative and IFN-γ–producing T Cell Memory to Smallpox in Humans . J Exp Med 7 June 2004; 199 (11): 1585–1593. doi: https://doi.org/10.1084/jem.20032083
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