In vitro responsiveness of gamma delta T cells from Mycobacterium bovis-infected cattle to mycobacterial antigens: Predominant involvement of WC1(+) cells

It is generally accepted that protective immunity against tuberculosis is g enerated through the cell-mediated immune (CMI) system, and a greater under standing of such responses is required if better vaccines and diagnostic te sts are to be developed, gamma delta T cells form a major proportion of the peripheral blood mononuclear cells (PBMC) in the ruminant system and, cons idering data from other species, may have a significant role in CMI respons es in bovine tuberculosis. This study compared the in vitro responses of al pha beta and gamma delta T cells from Mycobacterium bovis-infected and unin fected cattle. The results showed that, following 24 h of culture of PBMC w ith M. bovis-derived antigens, the majority of gamma delta T cells from inf ected animals became highly activated (upregulation of interleukin-2R), whi le a lower proportion of the alpha beta 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 gamma delta T cells rema ined significantly activated for at Feast 7 days in culture, while activati on of alpha beta T cells declined during that period. Subsequent analysis r evealed that the majority of activated gamma delta T cells expressed WC1, a 215-kDa surface molecule which is not expressed on human or murine gamma d elta T cells. Furthermore, in comparison with what was found for CD4(+) T c ells, M. bovis antigen was found to induce strong cellular proliferation bu t relatively little gamma interferon release by purified WC1(+) gamma delta T cells. Overall, while the role of these cells in protective immunity rem ains unclear, their highly activated status in response to M. bovis suggest s an important role in antimycobacterial Immunity, and the ability of gamma delta T cells to influence other immune cell functions remains to be eluci dated, particularly in relation to CMI-based diagnostic tests.