Cutting Edge: Antioxidative Properties of Myeloid Dendritic Cells: Protection of T Cells and NK Cells from Oxygen Radical-Induced Inactivation and Apoptosis

Abstract

Dendritic cells (DCs) communicate with nonadaptive and adaptive lymphocytes on multiple levels. Efficient DC-lymphocyte interactions require that lymphocytes remain viable and functional also under conditions of oxidative stress, such as in microbial infection or in the malignant microenvironment. For this study, we exposed human T and NK cells to oxidants delivered either by autologous phagocytes or in the form of exogenous hydrogen peroxide. In accordance with earlier studies, these lymphocytes became dysfunctional and subsequently apoptotic. The presence of myeloid DCs efficiently rescued T cells (CD4+ and CD8+) and NK cells from oxidant-induced inactivation and apoptosis. The mechanism of the myeloid DC-mediated lymphocyte protection was, at least in part, explained by the capacity of the myeloid DCs to neutralize extracellular oxygen radicals, which, in turn, was reversible upon coincubation with a catalase inhibitor. Our results are suggestive of a novel aspect of DC-lymphocyte interaction that may have implications for lymphocyte function in inflamed tissue.

Redox Remodeling by Dendritic Cells Protects Antigen-Specific T Cells against Oxidative Stress

“…Because immature DCs were highly efficient in inducing thiol expression in T cells, it seems reasonable to assume that the capacity of DCs to induce thiol expression in T cells cannot be further enhanced by maturation. These data are in accordance with a previous study showing that immature and mature DCs confer a similar level of protection from oxygen radical-induced inactivation to coincubated lymphocytes (20).…”

“…This study showed that DCs furnish effector T cells with cs-and ic-thiols during presentation of viral and bacterial Ags and that T cells with enhanced thiol expression consume ROS and escape oxidant-induced apoptosis. In accordance with previous studies (18,20), a slight, but significant, increase in thiol expression was observed on all T cells cocultured with DCs. However, using Ag-pulsed DCs and detection of Agspecific TCR/Vb regions or tetramer technology, we found that the DC-induced thiol expression was several-fold higher in T cells specific for the presented Ag.…”

“…However, expression of thiols reportedly promotes T cell function; for example, the presence of reduced intracellular thiols (ic-thiols) in T cells and thiols expressed in cell surface proteins (cs-thiols) improves T cell reactivity and proliferation (15)(16)(17). The purported function of thiols in T cell immunity is further bolstered by the findings that dendritic cells (DCs), which are prominent APCs, release thiols (18,19) and trigger thiol expression on adjacent cells, including NK cells and T cells (18,20).…”

“…The isolation procedures resulted in .98% pure cell populations. T and B cells were immediately frozen in CryoMaxx S. Purified monocytes were differentiated into DCs using IL-4 (500 U/ml) and GM-CSF (600 U/ml), as described (20).…”

T cell tyrosine phosphorylation response to transient redox stress

“…Besides the involvement of redox-sensitive NF-kB and Nrf2 transcription factors in T cell activation [68,69] and additional evidence indicating the involvement of ROS in T cell activation and proliferation [70][71][72], very limited information is currently available on the regulatory and signaling mechanisms involved in ROS response. To generate specific responses, ROS need to interact with molecular sensors, likely to be cysteine residues located in regulatory elements.…”