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

B Combadiere, A Boissonnas, G Carcelain… - The Journal of …, 2004 - rupress.org
B Combadiere, A Boissonnas, G Carcelain, E Lefranc, A Samri, F Bricaire, P Debre, B Autran
The Journal of experimental medicine, 2004rupress.org
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 …
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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