Potentiation of cytokine-induced proliferation of human Natural Killer cells by intravenous immunoglobulin G

Issekutz, Andrew C.; Käsermann, Fabian; Rowter, Derek

doi:10.1016/j.clim.2015.08.005

Cited by 4 publications

(3 citation statements)

References 69 publications

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“…We also saw an increase in the percentage of CD71 + CD56 dim NK cells after IVIG indicating increased proliferation of CD56 dim NK cells in this group of patients ( Figure 1 ). Previously, our group showed that stimulation of normal donor PBMCs in vitro with submitogenic concentrations of IL-2, IL-15 or IL-18, in the presence of IVIG induced selective NK cell proliferation ( 30 ). IVIG was also shown to drive NK cell proliferation in vivo in a mouse model of graft-versus-host disease, in which it was associated with suppression of the disease ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

et al. 2021

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Intravenous immunoglobulin (IVIG) is an effective immunomodulatory treatment for immune dysregulation diseases. However, the mechanisms by which it reduces systemic inflammation are not well understood. NK cell cytotoxicity is decreased by IVIG in women with reduced fertility, but IVIG effects on NK cells in immune dysregulation are less clear. We hypothesized that IVIG modulation of lymphocyte function, especially in NK cells, is important for resolution of inflammation. Our aim was to identify IVIG-induced changes in a cohort of patients with Kawasaki disease (KD) and those that occur broadly in pediatric patients with various immune dysregulatory diseases. Peripheral blood mononuclear cells (PBMCs) of patients with KD or autoimmune/inflammatory diseases were phenotyped pre and post high dose IVIG treatment by flow cytometry. In KD patients, after IVIG infusion Treg cell frequency and the proportion of activated CD25+ immunoregulatory CD56bright NK cells was increased, and multiple lymphocyte subsets showed increased expression of the lymphoid tissue homing receptor CD62L. Importantly, IVIG treatment decreased the frequency of cells expressing the degranulation marker CD107a among cytotoxic CD56dim NK cells, which was reflected in a significant reduction in target cell killing and in decreased production of multiple pro-inflammatory mediators. Interestingly, the activating receptor CD336 was expressed on a higher proportion of CD56bright NK cells after IVIG in both KD and autoimmune/inflammatory patients while other NK receptors were increased differentially in each cohort. In autoimmune/inflammatory patients IVIG induced the proliferation marker CD71 on a higher percentage of CD56dim NK cells, and in contrast to KD patients, CD107a+ cells were increased in this subset. Furthermore, when PBMCs were stimulated ex vivo with IL-2 or Candida antigen in autologous plasma, more of the CD4+ T cells of KD patients expressed CD25 after IVIG therapy but fewer cytotoxic T cells were degranulated based on CD107a expression. In summary, IVIG treatment in patients with immune dysregulation has multiple effects, especially on NK cell subsets and CD4+ T cells, which are compatible with promoting resolution of inflammation. These novel findings provide insight into the immunomodulatory actions of IVIG in autoimmune and inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

et al. 2021

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“…[62][63][64][65] However , IVIg with its multiple mechanisms of action that effects B-and T-cells and neutralizes cytokines complement and autoantibodies without significant long-term immunosuppression might offer an advantage compared to other modalities. [66,67] Neuropathy manifestations were seen in three patients in our case series. Demyelinating neuropathies, such as Guillain-Barre syndrome (GBS) or its variant Miller Fisher seen in case 5, are the more commonly described CPI neurotoxicities, and their management is focused on preventing respiratory failure, its most serious complication, [68] with PEx (5 cycles of 50 mL/kg over 1-2 weeks) and IVIg (0.4 g/kg daily for 5 days).…”

Section: Discussionmentioning

confidence: 53%

Neuromuscular Weakness Syndromes from Immune Checkpoint Inhibitors: A Case Series and Literature Review

Daher

Matsuoka

Loghin

et al. 2019

Journal of Immunotherapy and Precision Oncology

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Immune checkpoint inhibitors (CPIs) (anti-cytotoxic T-lymphocyte antigen-4, anti-programmed death 1, and anti-programmed death-ligand 1) have transformed the landscape of cancer therapy. However, their increasing use has unleashed immune-related adverse events in various organs, among which neurologic ones, while rare, are increasingly being recognized and remain incompletely characterized. Herein, we report five patients with nonmelanoma cancers who developed weakness after receiving CPIs. The etiology was attributed to radiculoneuritis (one patient), myositis (one patient), Miller Fisher/myasthenia gravis (MG) (one patient), neuropathy/myositis/MG (one patient), and myositis/MG (one patient). Weakness developed after a median of two doses (range: 1–3) and 4 weeks (range: 3–10) from initiation of therapy. Two patients had severe manifestations without improvement while the other three experienced partial improvement despite discontinuation of the CPI (s) and initiation of immunosuppressive therapy. A review of literature identified 62 similar cases. This report highlights the challenges in the diagnosis and management of neurologic adverse events related to the use of CPIs. It also addresses the crucial need for early recognition, proper workup, and better biomarkers to help improve the outcomes of these adverse events.

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“…Purified human NK cells cultured overnight in IL-2, IL-12, IL-15, and IL-18 that were subsequently infused into mice displayed increased responsiveness to exogenous IL-2; this was thought to be due to the induction of increased CD25 expression on the NK cells, a key component in the formation of the high-affinity IL-2 receptor subtype, IL-2Rαβγ ( 18 ). Many other combinations, including both cytokines—most recently IL-27—and other substances such as intravenous immunoglobulin, have been or are currently undergoing evaluation for their prospective roles in NK cell population modulation ( 14 , 19 , 20 ).…”

Section: Go Forth and Multiply!: Nk Cell Population Enhancementmentioning

confidence: 99%

Potentiation of Natural Killer Cells for Cancer Immunotherapy: A Review of Literature

Lowry

Zehring

2017

Front. Immunol.

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It is widely acknowledged that the human immune system plays a crucial role in preventing the formation and progression of innumerable types of cancer (1). The mechanisms by which this occurs are numerous, including contributions from both the innate and adaptive immune systems. As such, immunotherapy has long been believed to be an auspicious solution in the treatment of malignancy (2). Recent research has highlighted the promise of natural killer (NK) cells as a more directed immunotherapy approach. This paper will focus on the methods of potentiation of NK cells for their use in cancer therapy.

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Potentiation of cytokine-induced proliferation of human Natural Killer cells by intravenous immunoglobulin G

Cited by 4 publications

References 69 publications

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

Neuromuscular Weakness Syndromes from Immune Checkpoint Inhibitors: A Case Series and Literature Review

Potentiation of Natural Killer Cells for Cancer Immunotherapy: A Review of Literature

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