Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans

• Published in: The Journal of experimental medicine Vol. 199; no. 11; pp. 1585 - 1593
• Main Authors: Combadiere, Behazine, Boissonnas, Alexandre, Carcelain, Guislaine, Lefranc, Evelyne, Samri, Assia, Bricaire, François, Debre, Patrice, Autran, Brigitte
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 07.06.2004
• Subjects: Adult; Aged; Female; Humans; Immunologic Memory; Interferon-gamma - biosynthesis; Lymphocyte Activation; Male; Middle Aged; Smallpox Vaccine - immunology; T-Lymphocytes - immunology; Vaccination; Vaccinia virus - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20032083

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.