IL-12 Expands and Differentiates Human V γ2Vδ2 T Effector Cells Producing Antimicrobial Cytokines and Inhibiting Intracellular Mycobacterial Growth

Discussion To our knowledge, the current study provides new evidence that IL-12 helps to promote expansion and differentiation of HMBPP-activated Vγ2Vδ2 T cells through signaling activities involving PI3K/AKT and STAT4 and TNF-α pathways, but not p38/MAPK, IL-2, IFN-γ networks. Vγ2Vδ2 T cells expanded by HMBPP + IL-12 display a memory phenotype of rapid proliferation, produce/co-produce anti-microbial cytokines IFN-γ, TNF-α, GM-CSF, and CD107a, express the Mtb-killing tri-CTL cytotoxic granule molecules GZMB, GNLY, and PRF. Importantly, these expanded Vγ2Vδ2 T cells can inhibit intracellular BCG growth in autologous hMDM and THP-1 cells. These findings support the hypothesis that IL-12, a key innate cytokine produced by initial Mtb infection, helps to drive early development of fast-acting Vγ2Vδ2 T effector cells in anti-TB immune responses (10, 15, 16, 28). The IL-12 effects on Vγ2Vδ2 T cells have been evaluated in vitro in humans with HIV-1 infection (32, 39) and cancer (40). IL-12 helps to produce IFN-γ/TNF-α in the responder subset of HIV-1-infected humans, but fails to induce the activation of Vγ2Vδ2 T cells from anergic HIV-infected persons (32). While IL-12 and IL-18 synergize Vγ2Vδ2 T cell-mediated cytotoxicity against tumor cells (23), IL-18 enhances the proliferative and recall response of Vγ2V&...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research