Mycobacterium-Specific γ 9 δ 2 T Cells Mediate Both Pathogen-Inhibitory and CD40 Ligand-Dependent Antigen Presentation Effects Important for Tuberculosis Immunity

Abstract

ABSTRACT Numerous pathogens, including Mycobacterium tuberculosis , can activate human γ 9 δ 2 T cells to proliferate and express effector mechanisms. γ 9 δ 2 T cells can directly inhibit the growth of intracellular mycobacteria and may also act as antigen-presenting cells (APC). Despite evidence for γδ T cells having the capacity to function as APC, the mechanisms involved and importance of these effects on overall tuberculosis (TB) immunity are unknown. We prepared M. tuberculosis -specific γ 9 δ 2 T cell lines to study their direct protective effects and APC functions for M. tuberculosis -specific αβ T cells. The direct inhibitory effects on intracellular mycobacteria were measured, and the enhancing effects on proliferative and effector responses of αβ T cells assessed. Furthermore, the importance of cell-to-cell contact and soluble products for γ 9 δ 2 T cell effector responses and APC functions were investigated. We demonstrate, in addition to direct inhibitory effects on intracellular mycobacteria, the following: (i) γ 9 δ 2 T cells enhance the expansion of M. tuberculosis -specific αβ T cells and increase the ability of αβ T cells to inhibit intracellular mycobacteria; (ii) although soluble mediators are critical for the direct inhibitory effects of γ 9 δ 2 T cells, their APC functions do not require soluble mediators; (iii) the APC functions of γ 9 δ 2 T cells involve cell-to-cell contact that is dependent on CD40-CD40 ligand (CD40L) interactions; and (iv) fully activated CD4 + αβ T cells and γ 9 δ 2 T cells provide similar immune enhancing/APC functions for M. tuberculosis -specific T cells. These effector and helper effects of γ 9 δ 2 T cells further indicate that these T cells should be considered important new targets for new TB vaccines.