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In the absence of CD154, administration of interleukin-12 restores Th1 responses but not protective immunity to Schistosoma mansoni

Hewitson, James P., Hamblin, Paul A. and Mountford, Adrian P. (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

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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.

Item Type: Article
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
Academic Units: The University of York > Biology (York)
Depositing User: Sherpa Assistant
Date Deposited: 14 Sep 2007 14:37
Last Modified: 17 Oct 2013 14:14
Published Version: http://dx.doi.org/10.1128/IAI.00252-07
Status: Published
Refereed: Yes
Related URLs:
URI: http://eprints.whiterose.ac.uk/id/eprint/3363

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