Partial and Ineffective Activation of Vγ9Vδ2 T Cells by Mycobacterium tuberculosis-Infected Dendritic Cells

gamma delta T cells and dendritic cells (DCs) participate in early phases of immune response against Mycobacterium tuberculosis. We investigated whether a close functional relationship exists between these two cell populations using an in vitro coculture in a human system. V gamma 9V delta 2 T cells induce full maturation of M. tuberculosis-infected immature DCs, as demonstrated by upregulation of the costimulatory CD80, CD86, CD40, and HLA-DR molecules on infected DCs after 24 h of coculture. Reciprocally, infected DCs induced substantial activation of V gamma 9V delta 2 T cells upon coculture, which was cell-to-cell contact and TCR dependent, as demonstrated in transwell experiments. However, infected DCs selectively induced proliferative, but not cytokine or cytolytic, responses of V gamma 9V delta 2 T cells, and this was associated with the expansion of phenotypically immature, central memory-type V gamma 9V delta 2 T cells. Importantly, expansion of central memory V gamma 9V delta 2 T cells and reduction of the pool of V gamma 9V delta 2 T cells with immediate effector functions (effector memory and terminally differentiated cells) were also detected in vivo in the peripheral blood of patients with active tuberculosis, which reversed after antimycobacterial therapy. M. tuberculosis-infected DCs produced many different cytokines, but not IL-15, and addition of IL-15 to cocultures of infected DCs and V gamma 9V delta 2 T cells caused efficient differentiation of these latter with generation of effector memory and terminally differentiated cells, which were capable of reducing the viability of intracellular M. tuberculosis. Overall, this study provides a further piece of information on the complex relationship between important players of innate immunity during mycobacterial infection. The Journal of Immunology, 2010, 185: 1770-1776.