Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy
Dr. Francesco Dieli, Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Corso Tukory 211, 90134 Palermo, Italy. E-mail address: dieli@unipa.it
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. V9V2 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 V9V2 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 V9V2 T cells, and this was associated with the expansion of phenotypically immature, central memory-type V9V2 T cells. Importantly, expansion of central memory V9V2 T cells and reduction of the pool of V9V2 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 V9V2 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.
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