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Infection and Immunity, July 2007, p. 3539-3547, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00252-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In the Absence of CD154, Administration of Interleukin-12 Restores Th1 Responses but Not Protective Immunity to Schistosoma mansoni{triangledown}

James P. Hewitson,1,{dagger} Paul A. Hamblin,2 and Adrian P. Mountford1*

Department of Biology, University of York, York YO10 5YW, United Kingdom,1 Biopharmaceutical CEDD, GlaxoSmithKline, GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom2

Received 15 February 2007/ Accepted 29 April 2007

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.

* Corresponding author. Mailing address: Department of Biology (Area 5), University of York, York YO10 5YW, United Kingdom. Phone: 44-1904-328595. Fax: 4-1904-328599. E-mail: apm10{at}york.ac.uk

{triangledown} Published ahead of print on 7 May 2007.

Editor: W. A. Petri, Jr.

{dagger} Present address: Institute of Immunology and Infection Research, 101 Ashworth Laboratories, King's Buildings, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, United Kingdom.

Infection and Immunity, July 2007, p. 3539-3547, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00252-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • McManus, D. P., Loukas, A. (2008). Current Status of Vaccines for Schistosomiasis. Clin. Microbiol. Rev. 21: 225-242 [Abstract] [Full Text]  


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