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Infection and Immunity, March 1999, p. 1034-1044, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Generation of CD8+ T-Cell Responses to Mycobacterium bovis and Mycobacterial Antigen in Experimental Bovine Tuberculosis

Ernesto Liébana,1 Robert M. Girvin,2 Michael Welsh,2 Sydney D. Neill,2 and John M. Pollock2,*

Department of Veterinary Science, Queen's University of Belfast,1 and Veterinary Sciences Division, Department of Agriculture for Northern Ireland,2 Stormont, Belfast, Northern Ireland

Received 2 September 1998/Returned for modification 9 October 1998/Accepted 26 November 1998

Protective immunity against tuberculosis is considered to be essentially cell mediated, and an important role for CD8+ T lymphocytes has been suggested by several studies of murine and human infections. The present work, using an experimental model of infection with Mycobacterium bovis in cattle, showed that live M. bovis elicits the activation of CD8+ T cells in vitro. However, a sonic extract prepared from M. bovis (MBSE) and protein purified derivative (PPDb) also induced a considerable degree of activation of the CD8+ T cells. Analysis of proliferative responses of peripheral blood mononuclear cells, purified CD8+ T cells, and CD8+ T-cell clones to M. bovis and to soluble antigenic preparations (MBSE, PPDb) showed that the responses of all three types of cells were always superior for live mycobacteria but that strong responses were also obtained with complex soluble preparations. Furthermore, while cytotoxic capabilities were not investigated, the CD8+ T cells were found to produce and release gamma interferon in response to antigen (live and soluble), which indicated one possible protective mechanism for these cells in bovine tuberculosis. Finally, it was demonstrated by metabolic inhibition with brefeldin A and cytochalasin D at the clonal level that an endogenous pathway of antigen processing is required for presentation to bovine CD8+ cells and that presentation is also dependent on phagocytosis of the antigen.

* Corresponding author. Mailing address: Veterinary Sciences Division, Department of Agriculture for Northern Ireland, Stoney Rd., Stormont, Belfast BT4 3SD, Northern Ireland. Phone: 44-1232-525684. Fax: 44-1232-525 745. E-mail: pollockj{at}dani.gov.uk.

Infection and Immunity, March 1999, p. 1034-1044, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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