Comment on: Evidence of innate lymphoid cell redundancy in humans

Mace, Emily M.; French, Anthony R.; Yokoyama, Wayne M.; Fehniger, Todd A.; Cooper, Megan A.

doi:10.1038/s41590-018-0164-5

Cited by 9 publications

(5 citation statements)

References 12 publications

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“…The simultaneous impairment of T and NK cells occurring in several IEIs predisposing to severe EBV infection does not allow discerning the individual role of each cell type in the immune control of the virus. Moreover, there is an open discussion about the essential vs. redundant role of NK cells in host defense against EBV and, more generally, in human immunity [ 50 , 51 ]. On the one hand, a nonessential role for NK cells was put forward because T − NK − patients with severe combined immunodeficiency (SCID) who recovered T but not innate lymphoid cells after HSCT were not susceptible to severe EBV infection over a long follow-up period [ 52 ]; a further argument is that patients with IEIs that affect NK cell development and/or function (i.e., mutated GATA2 , MCM4 , RTEL1 , GINS1 , IRF8 , and FCGR3A ) and predispose to severe/fatal herpesvirus infections [ 12 ] might have defects in other immunological compartments, at least in some cases [ 38 , 51 ].…”

Section: Role Of Nk Cells In Primary Immunodeficiencies Predisposing ...mentioning

confidence: 99%

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

Desimio

Covino

Rivalta

et al. 2023

Cancers

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The Epstein–Barr virus (EBV) is a ubiquitous herpesvirus most often transmitted during infancy and infecting the vast majority of human beings. Usually, EBV infection is nearly asymptomatic and results in life-long persistency of the virus in a latent state under the control of the host immune system. Yet EBV can cause an acute infectious mononucleosis (IM), particularly in adolescents, and is associated with several malignancies and severe diseases that pose a serious threat to individuals with specific inborn error of immunity (IEI). While there is a general consensus on the requirement for functional CD8 T cells to control EBV infection, the role of the natural killer (NK) cells of the innate arm of immunity is more enigmatic. Here we provide an overview of the interaction between EBV and NK cells in the immunocompetent host as well as in the context of primary and secondary immunodeficiencies. Moreover, we report in vitro data on the mechanisms that regulate the capacity of NK cells to recognize and kill EBV-infected cell targets and discuss the potential of recently optimized NK cell-based immunotherapies for the treatment of EBV-associated diseases.

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Section: Role Of Nk Cells In Primary Immunodeficiencies Predisposing ...mentioning

confidence: 99%

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

Desimio

Covino

Rivalta

et al. 2023

Cancers

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“…Of note, the high prevalence of warts related to HPV infection observed in patients with SCID-X1 after HSCT and gene therapy (128) has been suggested to be associated with persistent NK defects (52). However, the clinical consequences of NK cell deficiency has been a matter of debate (44,(129)(130)(131), and alternative hypotheses to explain the prevalence of these infections in SCID-X1 patients have been put forward, including defective gc signaling in keratinocytes (128). In conclusion, promising results have been reported with the use of LVs and conditioning treatment regarding the NK-cell reconstitution, although long-term follow-up and results from other clinical trials, hopefully including more phenotypic and functional studies, are needed to confirm them.…”

Section: Nk Cellsmentioning

confidence: 99%

Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease

et al. 2020

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X-linked severe immunodeficiency disease (SCID-X1) is an inherited, rare, and life-threating disease. The genetic origin is a defect in the interleukin 2 receptor γ chain (IL2RG) gene and patients are classically characterized by absence of T and NK cells, as well as presence of partially-functional B cells. Without any treatment the disease is usually lethal during the first year of life. The treatment of choice for these patients is hematopoietic stem cell transplantation, with an excellent survival rate (>90%) if an HLA-matched sibling donor is available. However, when alternative donors are used, the success and survival rates are often lower. Gene therapy has been developed as an alternative treatment initially using γ-retroviral vectors to correct the defective γ chain in the absence of pre-conditioning treatment. The results were highly promising in SCID-X1 infants, showing long-term T-cell recovery and clinical benefit, although NK and B cell recovery was less robust. However, some infants developed T-cell acute lymphoblastic leukemia after the gene therapy, due to vector-mediated insertional mutagenesis. Consequently, considerable efforts have been made to develop safer vectors. The most recent clinical trials using lentiviral vectors together with a low-dose pre-conditioning regimen have demonstrated excellent sustained T cell recovery, but also B and NK cells, in both children and adults. This review provides an overview about the different gene therapy approaches used over the last 20 years to treat SCID-X1 patients, particularly focusing on lymphoid immune reconstitution, as well as the developments that have improved the process and outcomes.

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“…By way of introduction, NK cells are categorized as lymphocytes of the innate immune system as a divergent branch of the innate lymphoid cell (ILC) lineage [1]. These cells are not vestigial and have been sustained through evolution for a variety of reasons [2]. They are postulated to serve relevant roles in reproductive success, surveillance of cancerous cells and control of viral infections [3][4][5][6].…”

Section: Nkd-directed Primer On Nk Cell Biology and Functionmentioning

confidence: 99%

How I Manage Natural Killer Cell Deficiency

Orange

2019

J Clin Immunol

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Natural killer (NK) cell deficiency (NKD) is a subset of primary immunodeficiency disorders (PID) in which an abnormality of NK cells represents a major immunological defect resulting in the patient's clinical immunodeficiency. This is distinct from a much larger group of PIDs that include an NK cell abnormality as a minor component of the immunodeficiency. Patients with NKD most frequently have atypical consequences of herpesviral infections. There are now 6 genes that have been ascribed to causing NKD, some exclusively and others that also cause other known immunodeficiencies. This list has grown in recent years and as such the mechanistic and molecular clarity around what defines an NKD is an emerging and important field of research. Continued increased clarity will allow for more rational approaches to the patients themselves from a therapeutic standpoint. Having evaluated numerous individuals for NKD, I share my perspective on approaching the diagnosis and managing these patients.

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Comment on: Evidence of innate lymphoid cell redundancy in humans

Cited by 9 publications

References 12 publications

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease

How I Manage Natural Killer Cell Deficiency

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