Lack of cell movement impairs survival of peripheral blood IL-2-stimulated natural killer cells originating from solid cancer and promotes red blood cells to induce their switch toward a regulatory phenotype.

BACKGROUND: Red blood cells (RBCs) can have a modulatory effect on immune cells; so changes in their dynamism could considerably influence their physiology, and consequently the immune activities of neighbouring cells, like natural killer (NK) cells. Herein, we studied the effect of both RBCs and lack of cell movement on the proliferation, survival and regulation of peripheral IL-2-stimulated NK cells from normal and solid malignant conditions. METHODS: Experiments were conducted on twelve cell culture groups, including NK cells from patients with solid malignant tumor or healthy controls, cultured alone or with autologous or nonautologous RBCs under shaking or no shaking conditions. RESULTS: NK cells from neoplastic patients behaved differently depending on the culture conditions including shaking and/or RBCs presence. Therefore, NK cells survival was downregulated in the absence of shaking; whereas, shaking have not only upregulated cell survival, but also downregulated the levels of p53-related apoptosis. Moreover, RBCs enhanced NK cells proliferation; while, this effect was modulated by shaking. Furthermore, RBCs can generate opposite effects on the production and modulation of protumoral or immunosuppressive cytokines, depending on the origin of NK cells, i.e., whether they derive from healthy or solid malignant tumor conditions. Finally, NK cells become able to express Foxp3 regulatory marker when combining three main conditions that include (i) treatment with high dose of IL-2, (ii) presence of RBCs, and (iii) absence of shaking. CONCLUSIONS: Our outcomes showed for the first time that cell stagnation would be markedly involved in peripheral NK cell apoptosis, as well as in switching toward a regulatory phenotype-induced Foxp3. Cell movement may be one of ex vivo potential approaches in boosting the activities and survival of such cells during solid cancer.

Rituximab Treatment Modulates the Release of Hydrogen Peroxide and the Production of Proinflammatory Cytokines by Monocyte at the Onset of Type 1 Diabetes.

BACKGROUND: Monocytes are the main blood innate mononuclear phagocyte and one of the most important effector cells expressing Fcγ receptor, which is critical for the interaction with Fc domain of antibodies. OBJECTIVE: To evaluate the effect of Rituximab (RTX, a chimeric human anti-CD20 monoclonal antibody) on the functional activities of Monocytes (MOs) at the onset of human Type 1 Diabetes (T1D). METHODS: MOs were isolated from peripheral blood mononuclear cells (PBMCs) obtained from volunteer patients with recent-onset T1D and healthy control donors. RESULTS: The levels of the production of Interleukin 1ß (IL-1ß) and IL-6 were significantly increased in MOs from patients with T1D when compared to MOs from healthy controls (respectively, p < 0.01 and p < 0.05). Similarly, Interferon γ (IFN-γ), and intracellular free Calcium Ion (ifCa2+) levels were increased in T1D MOs than in control MOs, but the difference did not reach a significant level. Conversely, the production levels of IL-4 and catalase activity, as well as of both phagocytosis and killing capacities were decreased in MOs of T1D patients compared to MOs from healthy controls, but the difference was not significant for catalase activity and killing capacity (respectively, p < 0.01, p > 0.05, p < 0.01, and p > 0.05). Additionally, treatment with RTX significantly upregulated phagocytosis (p < 0.05), markedly downregulated the release of IL-1ß (p < 0.01), ifCa2+, hydrogen peroxide (H2O2), and slightly downregulated the Nitric Oxide Synthase (NOS) activity, NOS activity-to-arginase activity ratio, the levels of Lactate Dehydrogenase (LDH)-based cytotoxicity, and the production of IL-6 and IFN-γ. Moreover, RTX treatment significantly upregulated the production of IL-4 (p < 0.05), IL-10 (p < 0.01) and the catalase activity (p < 0.05). CONCLUSION: Our study has shown for the first time that RTX can reverse the abnormal functional activities of MOs as well as their production of proinflammatory cytokines at the onset of T1D. From a therapeutic point of view, RTX may potentially be suggested at the beginning of T1D to immunomodulate innate immunity and inflammatory conditions.