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

Combadiere B, Boissonnas A, Carcelain G, Lefranc E, Samri A, Bricaire F, Debre P, Autran B - J. Exp. Med. (2004)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie Cellulaire, INSERM U543, Paris, France.

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.

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Related in: MedlinePlus

Vaccinia-specific CD4 and CD8 memory cells. CD8-depleted PBMCs (grey bars) compared with total PBMCs (black bars) were tested by ELISpot assay (a) and proliferation assay (b). Results are shown for two representative individuals.
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fig2: Vaccinia-specific CD4 and CD8 memory cells. CD8-depleted PBMCs (grey bars) compared with total PBMCs (black bars) were tested by ELISpot assay (a) and proliferation assay (b). Results are shown for two representative individuals.

Mentions: To assess the cell populations involved in these vaccinia-specific responses, we first assayed IFN-γ production and proliferation after CD8 cell depletion (Fig. 2, a and b). Residual vaccinia-specific effector and proliferative responses were still observed in most vaccinated individuals; this suggests that CD4 T cells were the major component of these persistent effector–memory T cell responses. That absolute numbers of vaccinia-specific SFCs in the CD4-enriched PBMC fractions did not increase suggests that IFN-γ–producing CD8 cells were also involved.


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

Combadiere B, Boissonnas A, Carcelain G, Lefranc E, Samri A, Bricaire F, Debre P, Autran B - J. Exp. Med. (2004)

Vaccinia-specific CD4 and CD8 memory cells. CD8-depleted PBMCs (grey bars) compared with total PBMCs (black bars) were tested by ELISpot assay (a) and proliferation assay (b). Results are shown for two representative individuals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211784&req=5

fig2: Vaccinia-specific CD4 and CD8 memory cells. CD8-depleted PBMCs (grey bars) compared with total PBMCs (black bars) were tested by ELISpot assay (a) and proliferation assay (b). Results are shown for two representative individuals.
Mentions: To assess the cell populations involved in these vaccinia-specific responses, we first assayed IFN-γ production and proliferation after CD8 cell depletion (Fig. 2, a and b). Residual vaccinia-specific effector and proliferative responses were still observed in most vaccinated individuals; this suggests that CD4 T cells were the major component of these persistent effector–memory T cell responses. That absolute numbers of vaccinia-specific SFCs in the CD4-enriched PBMC fractions did not increase suggests that IFN-γ–producing CD8 cells were also involved.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie Cellulaire, INSERM U543, Paris, France.

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.

Show MeSH
Related in: MedlinePlus