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Infection and Immunity, March 2002, p. 1488-1500, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1488-1500.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Modulation of Immune Responses to Mycobacterium bovis in Cattle Depleted of WC1+ {gamma}{delta} T Cells

Hilary E. Kennedy,1 Michael D. Welsh,2 David G. Bryson,2 Joseph P. Cassidy,3 Fiona I. Forster,2 Christopher J. Howard,4 Robert A. Collins,4 and John M. Pollock2*

Department of Veterinary Science, Queen's University Belfast, Belfast BT7 1NN,1 Veterinary Sciences Division, The Department of Agriculture and Rural Development, Stormont, Belfast BT4 3SD,2 Department of Veterinary Pathology, University College, Dublin 4, Ireland, and ,3 Institute for Animal Health, Compton, Berks RG20 7NN, United Kingdom4

Received 25 April 2001/ Returned for modification 6 June 2001/ Accepted 1 November 2001

It is accepted that cell-mediated immune responses predominate in mycobacterial infections. Many studies have shown that CD4+ T cells produce Th1 cytokines, such as gamma interferon (IFN-{gamma}), in response to mycobacterial antigens and that the cytolytic activity of CD8+ cells toward infected macrophages is important. However, the extent and manner in which {gamma}{delta} T cells participate in this response remain unclear. In ruminants, {gamma}{delta} T cells comprise a major proportion of the peripheral blood mononuclear cell population. We have previously shown that WC1+ {gamma}{delta} T cells are involved early in Mycobacterium bovis infection of cattle, but their specific functions are not well understood. Here we describe an in vivo model of bovine tuberculosis in which the WC1+ {gamma}{delta} T cells were depleted from the peripheral circulation and respiratory tract, by infusion of WC1+-specific monoclonal antibody, prior to infection. While no effects on disease pathology were observed in this experiment, results indicate that WC1+ {gamma}{delta} T cells, which become significantly activated (CD25+) in the circulation of control calves from 21 days postinfection, may play a role in modulating the developing immune response to M. bovis. WC1+-depleted animals exhibited decreased antigen-specific lymphocyte proliferative response, an increased antigen-specific production of interleukin-4, and a lack of specific immunoglobulin G2 antibody. This suggests that WC1+ {gamma}{delta} TCR+ cells contribute, either directly or indirectly, toward the Th1 bias of the immune response in bovine tuberculosis—a hypothesis supported by the decreased innate production of IFN-{gamma}, which was observed in WC1+-depleted calves.

* Corresponding author. Mailing address: Department of Bacteriology, Veterinary Sciences Division, The Department of Agriculture and Rural Development, Stormont, Belfast BT4 3SD, United Kingdom. Phone: 44 28 90 525684. Fax: 44 28 90 525745. E-mail: john.pollock{at}dardni.gov.uk.

Infection and Immunity, March 2002, p. 1488-1500, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1488-1500.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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