Human V gamma 2V delta 2 T cells produce IFN-gamma and TNF-alpha with an on/off/on cycling pattern in response to live bacterial products

Whereas cytokine production in alpha beta T cells is rapidly regulated by e xposure to peptide Ag, the mechanisms regulating cytokine production by gam ma delta T cells are unknown. In this study, we demonstrate that human V ga mma 2V delta2 T cells produce IFN-gamma and TNF-alpha as early as 2 h after Ag exposure, and that they produce these cytokines in a dose- and time- de pendent manner in response to stimulation with a live bacterial product, is o-butylamine (IBA), but not to dead bacteria or LPS. gamma delta T cells be gan, ceased, and then resumed IFN-gamma and TNF-alpha generation in an on/o ff/on cycling pattern, both in vitro and in vivo, depending on the presence or absence of IBA. IFN-gamma and TNF-alpha, whose optimum production was d ependent on IBA-stimulated gamma delta T cells, were critical for monocyte- mediated killing of Escherichia coli. By limiting cytokine production to pe riods of direct contact with live bacteria, gamma delta T cells focus their resources at the site of infection, while limiting systemic immunopatholog y. Thus, human gamma delta T cells may mediate innate resistance to extrace llular bacteria via tightly regulated cytokine production without necessari ly expanding in number.