Interleukin‐12 activates human γδ T cells: synergistic effect of tumor necrosis factor‐α

Abstract

gammadelta T cell populations are known to expand in response to intracellular bacterial infectious agents regardless of previous priming. We have shown previously that soluble factor(s) produced by Mycobacterium-stimulated monocytes activate cord blood gammadelta T cells to proliferate. In this study, we investigated whether cytokines produced by monocytes are responsible for gammadelta T cell activation in vitro: interleukin (IL)-1beta, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor were examined. Recombinant human IL-12 stimulated gammadelta T cells, but not alphabeta T cells in peripheral blood mononuclear cells, to express CD25 on their surfaces, and to expand in number in vitro. IL-12-primed gammadelta T cell numbers increased to a greater extent in the culture to which exogenous IL-2 (5 U/ml) was added. Anti-TNF-alpha monoclonal antibody inhibited IL-12-induced up-regulation of CD25 on gammadelta T cells, suggesting that endogenous TNF-alpha may play a role in IL-12-induced activation of gammadelta T cells. Recombinant TNF-alpha synergistically augmented IL-12-induced activation of gammadelta T cells. Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both. It also became evident that both IL-12 and TNF-alpha were produced by mycobacterial lysate-stimulated monocytes. Taken together, these results suggest that upon confrontation with mycobacterial organisms, gammadelta T cells can be quickly and antigen-nonspecifically activated by soluble factors including IL-12 and TNF-alpha, both of which are produced by mononuclear phagocytes in response to mycobacterial organisms.

Intrapulmonary TNF Gene Therapy Reverses Sepsis-Induced Suppression of Lung Antibacterial Host Defense

“…In addition to TNF, we also observed a significant increase in the production of IL-12 in the lung. TNF has been shown to enhance IL-12 production from NK and T cells previously (65,66). Given that IL-12 is a potent inducer of IFN-␥, it is quite likely that beneficial effects of adTNF in vivo are in part attributable to activating effects of cytokine networks initiated by TNF.…”

Expression of Toll-Like Receptor 2 on γδ T Cells Bearing Invariant Vγ6/Vδ1 Induced byEscherichia coliInfection in Mice

“…Analysis gate was set as described in Fig. 1 T cell proliferation (53). We have previously reported that ␥␦ T cells proliferate in response to IL-15 in vitro (37,54).…”

Immunopathologic Effects of Tumor Necrosis Factor Alpha in Murine Mycobacterial Infection Are Dose Dependent

“…2). In addition, TNF-␣ activates T cells or T-cell subsets, thereby facilitating the generation of cytokines and/or cytotoxic effector molecules and ensuring their sustained expression by the cells (11,30). TNF-␣ also activates and fosters differentiation of dendritic cells for enhanced IL-12 production and antigen presentation (11).…”