Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 14, 2014
Publication Date: March 1, 2014
Citation: McGill, J.L., Sacco, R.E., Baldwin, C.L., Telfer, J.C., Palmer, M.V., Waters, W.R. 2014. Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis. Journal of Immunology. 192(6):2756-2769. doi.org/10.4049/jimmunol.1302567. Interpretive Summary: Bovine tuberculosis causes considerable economic hardship to the livestock industry and represents a significant public health threat worldwide. Cattle have several subsets of T cells, one being gamma delta T cells. The different role of these T cell subsets in the immune response to Mycobacterium bovis, the causative agent of bovine tuberculosis, is unknown. Bovine gamma delta T cell subsets were purified from animals infected with M. bovis and analyzed for their ability to respond to mycobacterial products. The T cells responded to M. bovis infection, and there was a difference in the role of individual subsets in this immune response. This is the first demonstration of a unique role for individual gamma delta T cell subsets in the response against bovine tuberculosis. Additional research is needed to understand the role of individual T cell subsets in the bovine.
Technical Abstract: Promoting effective immunity to Mycobacterium bovis infection is a challenge that is of interest to the fields of human and animal medicine alike. We report that 'd T cells from virulent M. bovis infected cattle respond specifically and directly to complex, protein and non-protein mycobacterial antigens. Importantly, we demonstrate for the first time that bovine 'd T cells specifically recognize small peptide antigens derived from the mycobacterial protein complex early secreted antigenic target 6 kDa protein:10 kDa culture filtrate protein (ESAT6:CFP10) and that this recognition requires direct contact with APC, but is independent of MHC class II. Furthermore, we show that M. bovis infection in cattle induces robust IL-17A protein responses. Interestingly, in contrast to results from mice, bovine CD4 T cells and not 'd T cells, are the primary source of this critical pro-inflammatory mediator. Bovine 'd T cells are divided into subsets based upon their expression of Workshop Cluster 1 (WC1). We demonstrate that the M. bovis-specific 'd T cell response is composed of a heterogeneous mix of WC1-expressing populations, with WC1.1+ and WC1.2+ subsets responding in vitro to mycobacterial antigens, and both subsets accumulating in the lesions of M. bovis infected animals. The results described herein enhance our understanding of 'd T cell biology and, as virulent M. bovis infection of cattle represents an excellent model of tuberculosis in humans, contribute to our overall understanding of the role of 'd T cells in the mycobacterial-specific immune response.