Hewitson, James P orcid.org/0000-0002-3265-6763, Hamblin, Paul A and Mountford, Adrian P orcid.org/0000-0001-7675-1036 (2007) In the absence of CD154, administration of interleukin-12 restores Th1 responses but not protective immunity to Schistosoma mansoni. Infection and Immunity. pp. 3539-3547. ISSN 1098-5522
Abstract
The cytokine interplay during the development of protective immunity to the radiation-attenuated (RA) schistosome vaccine has been extensively characterized over recent years, yet the role of costimulatory molecules in the development of cell-mediated immunity is much less well understood. Here we demonstrate the importance of CD40/CD154 in vaccine-induced immunity, as CD154(-/-) mice exposed to RA schistosomes develop no protection to challenge infection. We showed that vaccinated CD154(-/-) mice have defective Th1-associated immune responses in the skin-draining lymph nodes and the lungs, with reduced or absent levels of interleukin-12p40 (IL-12p40), gamma interferon, and nitric oxide, but elevated levels of lung IL-4 and IL-5. The expression of major histocompatibility complex II (MHC-II) on antigen-presenting cells recovered from the lungs of vaccinated CD154(-/-) mice was also severely compromised. The administration of anti-CD40 monoclonal antibody (MAb) to CD154(-/-) mice did not reconstitute sustained Th1 responses in the lymph nodes or the lungs, nor did the MAb restore anti-parasite immunoglobulin G production or protective immunity. On the other hand, the administration of recombinant IL-12 (rIL-12) to CD154(-/-) mice shortly after vaccination caused elevated and sustained levels of Th1-associated cytokines, rescued MHC-II expression by lung CD11c(+) cells, and restored the appearance of inflammatory effector foci in the lungs. However, the treatment of CD154(-/-) mice with rIL-12 did not restore protection. We conclude that protective immunity to the RA schistosome vaccine is CD154 dependent but is independent of IL-12-orchestrated cellular immune mechanisms in the lungs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © 2007 by the American Society for Microbiology. This is an author produced version of a paper subsequently published in Infection and Immunity. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | LEISHMANIA-MAJOR INFECTION,VACCINE-INDUCED IMMUNITY,DEFICIENT MICE REVEAL,DRAINING LYMPH-NODES,T-CELL-ACTIVATION,DENDRITIC CELLS,CD40 LIGAND,NITRIC-OXIDE,IFN-GAMMA,CD40/CD154 INTERACTIONS |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Sherpa Assistant |
Date Deposited: | 14 Sep 2007 14:37 |
Last Modified: | 26 Nov 2024 00:21 |
Published Version: | https://doi.org/10.1128/IAI.00252-07 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1128/IAI.00252-07 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:3363 |