The radiation-attenuated schistosome vaccine induces high levels of protective immunity in the absence of B cells

TY - JOUR

T1 - The radiation-attenuated schistosome vaccine induces high levels of protective immunity in the absence of B cells

AU - Anderson, S

AU - Coulson, P S

AU - Ljubojevic, S

AU - Mountford, A P

AU - Wilson, R A

N1 - Open access copy available from the journal web site.

PY - 1999/1

Y1 - 1999/1

N2 - Radiation-attenuated cercariae of Schistosoma mansoni elicit consistently high levels of protective immunity in mice. The cell-mediated pulmonary effector mechanisms have been well characterized but the role of B cells and antibodies remains ill defined. We have compared the immune responses of B-cell-deficient (µMT) mice and their wild-type (WT) counterparts following exposure to the attenuated vaccine. Both groups mounted a T helper type 1 (Th1)-biased response in the skin-draining lymph nodes after vaccination. Interferon-¿ was the dominant cytokine secreted by airway leucocytes after challenge in both µMT and WT mice, but there was a somewhat greater Th2 component in the former animals. The cellular infiltrates observed in the airways, and the pulmonary effector foci, were of similar composition in the two groups although some large foci were present in the µMT mice. There was a marked dichotomy in the protection induced in µMT animals by a single vaccination, with two-thirds showing levels similar to their WT counterparts, demonstrating that cell-mediated mechanisms alone can provide adequate protection. The remaining µMT mice had a mean worm burden identical to that of their challenge controls. A possible explanation is that a proportion of the µMT animals have a genetic defect closely associated with the µ-heavy-chain locus on chromosome 12, which affects their ability to mount a protective cell-mediated response. Three vaccinations enhanced the immunity of WT animals, most likely by augmenting antibody-mediated mechanisms. In contrast, no enhancement was seen in µMT mice, suggesting that the cell-mediated response is not boosted by multiple exposures to attenuated larvae.

AB - Radiation-attenuated cercariae of Schistosoma mansoni elicit consistently high levels of protective immunity in mice. The cell-mediated pulmonary effector mechanisms have been well characterized but the role of B cells and antibodies remains ill defined. We have compared the immune responses of B-cell-deficient (µMT) mice and their wild-type (WT) counterparts following exposure to the attenuated vaccine. Both groups mounted a T helper type 1 (Th1)-biased response in the skin-draining lymph nodes after vaccination. Interferon-¿ was the dominant cytokine secreted by airway leucocytes after challenge in both µMT and WT mice, but there was a somewhat greater Th2 component in the former animals. The cellular infiltrates observed in the airways, and the pulmonary effector foci, were of similar composition in the two groups although some large foci were present in the µMT mice. There was a marked dichotomy in the protection induced in µMT animals by a single vaccination, with two-thirds showing levels similar to their WT counterparts, demonstrating that cell-mediated mechanisms alone can provide adequate protection. The remaining µMT mice had a mean worm burden identical to that of their challenge controls. A possible explanation is that a proportion of the µMT animals have a genetic defect closely associated with the µ-heavy-chain locus on chromosome 12, which affects their ability to mount a protective cell-mediated response. Three vaccinations enhanced the immunity of WT animals, most likely by augmenting antibody-mediated mechanisms. In contrast, no enhancement was seen in µMT mice, suggesting that the cell-mediated response is not boosted by multiple exposures to attenuated larvae.

KW - IRRADIATED CERCARIAE

KW - LYMPHOCYTES-T

KW - MANSONI INFECTION

KW - MICE

KW - MECHANISMS

KW - RESPONSES

KW - RECRUITMENT

KW - RESISTANCE

KW - PROLIFERATION

KW - DEFICIENT

U2 - 10.1046/j.1365-2567.1999.00661.x.

DO - 10.1046/j.1365-2567.1999.00661.x.

M3 - Article

VL - 96

SP - 22

EP - 28

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 1

ER -