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Infection and Immunity, November 2002, p. 6114-6120, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6114-6120.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Responses of Bovine WC1⁺ T Cells to Protein and Nonprotein Antigens of Mycobacterium bovis

Michael D. Welsh,^1* Hilary E. Kennedy,² Allister J. Smyth,² R. Martyn Girvin,¹ Peter Andersen,³ and John M. Pollock¹

Veterinary Sciences Division, The Department of Agriculture and Rural Development,¹ Department of Veterinary Science, Queen's University of Belfast, Stormont, Belfast BT4 3SD, United Kingdom,² Statens Serum Institut, 2300 Copenhagen S, Denmark³

Received 26 November 2001/ Returned for modification 8 March 2002/ Accepted 25 July 2002

WC1⁺ T cells of Mycobacterium bovis-infected cattle are highly responsive to M. bovis sonic extract (MBSE). In mycobacterial infections of other species, T cells have been shown to respond to protein and nonprotein antigens, but the bovine WC1⁺ T-cell antigenic targets within MBSE require further definition in terms of the dominance of protein versus nonprotein components. The present study sought to characterize the WC1⁺ T-cell antigenic targets, together with the role of interleukin-2 (IL-2), in the context of M. bovis infection. This was achieved by testing crude and defined antigens to assess protein versus nonprotein recognition by WC1⁺ T cells in comparison with CD4⁺ ß T cells. Both cell types proliferated strongly in response to MBSE, with CD4⁺ T cells being the major producers of gamma interferon (IFN-). However, enzymatic digestion of the protein in MBSE removed its ability to stimulate CD4⁺ T-cell responses, whereas some WC1⁺ T-cell proliferation remained. The most antigenic protein inducing proliferation and IFN- secretion in WC1⁺ T-cell cultures was found to be ESAT-6, which is a potential novel diagnostic reagent and vaccine candidate. In addition, WC1⁺ T-cell proliferation was observed in response to stimulation with prenyl pyrophosphate antigens (isopentenyl pyrophosphate and monomethyl phosphate). High levels of cellular activation (CD25 expression) resulted from MBSE stimulation of WC1⁺ T cells from infected animals. A similar degree of activation was induced by IL-2 alone, but for WC1⁺ T-cell division IL-2 was found to act only as a costimulatory signal, enhancing antigen-driven responses. Overall, the data indicate that protein antigens are important stimulators of WC1⁺ T-cell proliferation and IFN- secretion in M. bovis infection, with nonprotein antigens inducing significant proliferation. These findings have important implications for diagnostic and vaccine development.

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* Corresponding author. Mailing address: Department of Bacteriology, Veterinary Sciences Division, The Department of Agriculture and Rural Development, Stoney Rd., Stormont, Belfast BT4 3SD, United Kingdom. Phone: 44(0)28-90-525642. Fax: 44(0)28-90-525745. E-mail: michael.welsh{at}dardni.gov.uk.

Editor: S. H. E. Kaufmann

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Infection and Immunity, November 2002, p. 6114-6120, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6114-6120.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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