V gamma 9V delta 2 T cells impair intracellular multiplication of Brucellasuis in autologous monocytes through soluble factor release and contact-dependent cytotoxic effect

Human V gamma 9V delta2 T cells are considered to play an important role in brucellosis, as this population is dramatically increased in peripheral bl ood of patients during the acute phase of the infection. This T lymphocyte population has been largely demonstrated to be activated by small m.w. nonp eptidic molecules from natural or synthetic origin, We recently identified a nonpeptidic fraction of Brucella suis that specifically activates human V gamma 9V delta2 T cells, Using a two-separate-chambers system, we showed t hat Brucella fraction, as well as isopentenyl pyrophosphate-activated V gam ma 9V delta2 T cells, impaired the multiplication of B, suis in differentia ted THP-1 cells through TNF-alpha and IFN-gamma release. In the present stu dy, using circulating V gamma 9V delta2 T cells and autologous monocytes In fected with B. suis, we provide evidence that 1) intramonocytic multiplicat ion of B, suis is impaired by supernatants of activated V gamma 9V delta2 T cells in part via TNF-alpha and IFN-gamma thisimpairment occurring without host cell lysis; 2) unstimulated V gamma 9V delta2 T cells can impair intr acellular bacterial multiplication after their activation by soluble factor s released by infected monocytes; and 3) activated V gamma 9V delta2 T cell s lyse Brucella-infected monocytes in a contact-dependent manner, Taken tog ether, these results provide evidence that V gamma 9V delta2 T cells, in ad dition to being directly activated by soluble nonpeptidic molecules, can be stimulated to become highly cytotoxic in the specific presence of infected monocytes; moreover, they suggest how V gamma 9V delta2 T cells could be t riggered and respond as antibacterial effector cells in the early stages of Brucella infection.