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Journal of Virology, April 2009, p. 3626-3636, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02613-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Foot-and-Mouth Disease Virus Can Induce a Specific and Rapid CD4+ T-Cell-Independent Neutralizing and Isotype Class-Switched Antibody Response in Naïve Cattle{triangledown} ,{dagger}

Nicholas Juleff,1,2* Miriam Windsor,1 Eric A. Lefevre,3 Simon Gubbins,1 Pip Hamblin,1 Elizabeth Reid,1 Kerry McLaughlin,1 Peter C. L. Beverley,4 Ivan W. Morrison,2 and Bryan Charleston1

Pirbright Laboratory, Institute for Animal Health, Ash Road, Woking, Surrey GU24 0NF, United Kingdom,1 Centre for Tropical Veterinary Medicine, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, United Kingdom,2 Compton Laboratory, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, United Kingdom,3 the Edward Jenner Institute for Vaccine Research, University of Oxford, Compton, Newbury, Berkshire RG20 7NN, United Kingdom4

Received 18 December 2008/ Accepted 19 January 2009

The role of T-lymphocyte subsets in recovery from foot-and-mouth disease virus (FMDV) infection in calves was investigated by administering subset-specific monoclonal antibodies. The depletion of circulating CD4+ or WC1+ {gamma}{delta} T cells was achieved for a period extending from before challenge to after resolution of viremia and peak clinical signs, whereas CD8+ cell depletion was only partial. The depletion of CD4+ cells was also confirmed by analysis of lymph node biopsy specimens 5 days postchallenge. Depletion with anti-WC1 and anti-CD8 antibodies had no effect on the kinetics of infection, clinical signs, and immune responses following FMDV infection. Three of the four CD4+ T-cell-depleted calves failed to generate an antibody response to the nonstructural polyprotein 3ABC but generated a neutralizing antibody response similar to that in the controls, including rapid isotype switching to immunoglobulin G antibody. We conclude that antibody responses to sites on the surface of the virus capsid are T cell independent, whereas those directed against the nonstructural proteins are T cell dependent. CD4 depletion was found to substantially inhibit antibody responses to the G-H peptide loop VP1135-156 on the viral capsid, indicating that responses to this particular site, which has a more mobile structure than other neutralizing sites on the virus capsid, are T cell dependent. The depletion of CD4+ T cells had no adverse effect on the magnitude or duration of clinical signs or clearance of virus from the circulation. Overall, we conclude that CD4+ T-cell-independent antibody responses play a major role in the resolution of foot-and-mouth disease in cattle.

* Corresponding author. Mailing address: Pirbright Laboratory, Institute for Animal Health, Ash Road, Woking, Surrey GU24 0NF, United Kingdom. Phone: 44(0) 1483 232441. Fax: 44(0) 1483 232448. E-mail: nicholas.juleff{at}bbsrc.ac.uk

{triangledown} Published ahead of print on 28 January 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, April 2009, p. 3626-3636, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02613-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tomley, F. M., Shirley, M. W. (2009). Livestock infectious diseases and zoonoses. Phil Trans R Soc B 364: 2637-2642 [Abstract] [Full Text]  
  • Paton, D. J., Sumption, K. J., Charleston, B. (2009). Options for control of foot-and-mouth disease: knowledge, capability and policy. Phil Trans R Soc B 364: 2657-2667 [Abstract] [Full Text]  


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