In Vitro Responsiveness of γδ T Cells fromMycobacterium bovis-Infected Cattle to Mycobacterial Antigens: Predominant Involvement of WC1+Cells

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Abstract
It is generally accepted that protective immunity against tuberculosis is generated through the cell-mediated immune (CMI) system, and a greater understanding of such responses is required if better vaccines and diagnostic tests are to be developed. γδ T cells form a major proportion of the peripheral blood mononuclear cells (PBMC) in the ruminant system and, considering data from other species, may have a significant role in CMI responses in bovine tuberculosis. This study compared the in vitro responses of αβ and γδ T cells fromMycobacterium bovis-infected and uninfected cattle. The results showed that, following 24 h of culture of PBMC withM. bovis-derived antigens, the majority of γδ T cells from infected animals became highly activated (upregulation of interleukin-2R), while a lower proportion of the αβ T-cell population showed activation. Similar responses were evident to a lesser degree in uninfected animals. Study of the kinetics of this response showed that γδ T cells remained significantly activated for at least 7 days in culture, while activation of αβ T cells declined during that period. Subsequent analysis revealed that the majority of activated γδ T cells expressed WC1, a 215-kDa surface molecule which is not expressed on human or murine γδ T cells. Furthermore, in comparison with what was found for CD4+T cells,M. bovisantigen was found to induce strong cellular proliferation but relatively little gamma interferon release by purified WC1+γδ T cells. Overall, while the role of these cells in protective immunity remains unclear, their highly activated status in response toM. bovissuggests an important role in antimycobacterial immunity, and the ability of γδ T cells to influence other immune cell functions remains to be elucidated, particularly in relation to CMI-based diagnostic tests.

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