Virus-induced natural killer cell lysis of T cell subsets

Daniels, Keith A.; O’Donnell, Carey L.; Castonguay, Catherine; Strutt, Tara M.; McKinstry, K. Kai; Swain, Susan L.; Welsh, Raymond M.

doi:10.1016/j.virol.2019.10.003

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…Whereas this NK cell activity is performed to prevent fatal pathology, it has been suggested that in the case of patients with a chronic viral infection, NK cell depletion might restore the anti-viral immune function, enhancing viral control [103]. Moreover, the preferential elimination of different T cell subsets by NK cells has been analyzed, and it was found that T-reg, Th17, and Th2 cells were more sensitive than Th0 and Th1 cells [104]. Of interest, not only NK cells eliminate T cells to prevent fatal tissue pathology, but T-reg cells can also eliminate NK cells [85] to avoid an exacerbated inflammatory response with fatal consequences.…”

Section: Coordinated Immune Response After Viral Infectionsmentioning

confidence: 99%

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Bachiller

Battram

Perez-Amill

et al. 2020

Cancers

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Natural killer (NK) cells are potent anti-tumor and anti-microbial cells of our innate immune system. They are equipped with a vast array of receptors that recognize tumor cells and other pathogens. The innate immune activity of NK cells develops faster than the adaptive one performed by T cells, and studies suggest an important immunoregulatory role for each population against the other. The association, observed in acute myeloid leukemia patients receiving haploidentical killer-immunoglobulin-like-receptor-mismatched NK cells, with induction of complete remission was the determinant to begin an increasing number of clinical studies administering NK cells for the treatment of cancer patients. Unfortunately, even though transfused NK cells demonstrated safety, their observed efficacy was poor. In recent years, novel studies have emerged, combining NK cells with other immunotherapeutic agents, such as monoclonal antibodies, which might improve clinical efficacy. Moreover, genetically-modified NK cells aimed at arming NK cells with better efficacy and persistence have appeared as another option. Here, we review novel pre-clinical and clinical studies published in the last five years administering NK cells as a monotherapy and combined with other agents, and we also review chimeric antigen receptor-modified NK cells for the treatment of cancer patients. We then describe studies regarding the role of NK cells as anti-microbial effectors, as lessons that we could learn and apply in immunotherapy applications of NK cells; these studies highlight an important immunoregulatory role performed between T cells and NK cells that should be considered when designing immunotherapeutic strategies. Lastly, we highlight novel strategies that could be combined with NK cell immunotherapy to improve their targeting, activity, and persistence.

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Section: Coordinated Immune Response After Viral Infectionsmentioning

confidence: 99%

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Bachiller

Battram

Perez-Amill

et al. 2020

Cancers

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“…More recent studies on innate and specific immune responses in LCMV infection provided a new perspective on molecular mechanisms of immune responses with particular emphasis on recognition of LCMV and initiation of innate immune responses including type I IFNs and NK-cells. In addition, LCMV model made an important contribution in studies on the mechanisms of specific immunity, particularly thymic depletion in viral infection, modulation of Treg compartment, metabolic changes associated with chronic viral infection and mechanisms of indirect antibody-mediated protection (summarized in Table 3) [102][103][104][105][106][107][108].…”

Section: Lcmv Infection In Mice As An Immunological Modelmentioning

confidence: 99%

Lymphocytic Choriomeningitis—Emerging Trends of a Neglected Virus: A Narrative Review

et al. 2021

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Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent-borne zoonotic virus distributed worldwide. Since serologic assays are limited to several laboratories, the disease has been underreported, often making it difficult to determine incidence and seroprevalence rates. Although human clinical cases are rarely recorded, LCMV remains an important cause of meningitis in humans. In addition, a fatal donor-derived LCMV infection in several clusters of solid organ transplant recipients further highlighted a pathogenic potential and clinical significance of this virus. In the transplant populations, abnormalities of the central nervous system were also found, but were overshadowed by the systemic illness resembling the Lassa hemorrhagic fever. LCMV is also an emerging fetal teratogen. Hydrocephalus, periventricular calcifications and chorioretinitis are the predominant characteristics of congenital LCMV infection, occurring in 87.5% of cases. Mortality in congenitally infected children is about 35%, while 70% of them show long-term neurologic sequelae. Clinicians should be aware of the risks posed by LCMV and should consider the virus in the differential diagnosis of aseptic meningitis, especially in patients who reported contact with rodents. Furthermore, LCMV should be considered in infants and children with unexplained hydrocephalus, intracerebral calcifications and chorioretinitis. Despite intensive interdisciplinary research efforts, efficient antiviral therapy for LCMV infection is still not available.

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“…Th0 and Th1 cells the most resistant and regulatory T cell (Treg), Th17, Th2, and CD8 T cells the more sensitive to NK cell cytotoxicity. 46 Other viral infections also provided evidence for a regulatory role of NK cells. Depletion of NK cells in murine cytomegalovirus (MCMV)-infected mice resulted in enhanced IFN-production by CD4 and CD8 T cells, and CD8 T cell proliferation.…”

Section: Regulatory Functions Of Nk Cells During Viral Infectionsmentioning

confidence: 99%

“…More recently, it was observed that LCMV‐activated NK cells can kill all activated CD4 subsets and CD8 T cell in vitro and in vivo in a perforin‐dependent manner, yet the different T cell subsets showed a hierarchy of sensitivity, being. Th0 and Th1 cells the most resistant and regulatory T cell (Treg), Th17, Th2, and CD8 T cells the more sensitive to NK cell cytotoxicity 46 …”

Section: Regulatory Functions Of Nk Cells During Infectionsmentioning

confidence: 99%

Regulatory functions of NK cells during infections and cancer

Zwirner

Domaica

Fuertes

2020

Journal of Leukocyte Biology

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After recognition, NK cells can kill susceptible target cells through perforin-dependent mechanisms or by inducing death receptor-mediated apoptosis, and they can also secrete cytokines that are pivotal for immunomodulation. Despite the critical role as effector cells against tumors and virus-infected cells, NK cells have been implicated in the regulation of T cell-mediated responses in different models of autoimmunity, transplantation, and viral infections. Here, we review the mechanisms described for NK cell-mediated inhibition of adaptive immune responses, with spotlight on the emerging evidence of their regulatory role that shapes antitumor immune responses.

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Virus-induced natural killer cell lysis of T cell subsets

Cited by 6 publications

References 37 publications

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Lymphocytic Choriomeningitis—Emerging Trends of a Neglected Virus: A Narrative Review

Regulatory functions of NK cells during infections and cancer

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