Disseminated Varicella Infection Due to the Vaccine Strain of Varicella‐Zoster Virus, in a Patient with a Novel Deficiency in Natural Killer T Cells

Levy, Ofer; Orange, Jordan S.; Hibberd, Patricia L.; Steinberg, Sharon; LaRussa, Phillip; Weinberg, Adriana; Wilson, S. Brian; Shaulov, Angela; Fleisher, Gary; Geha, Raif S.; Bonilla, Francisco A.; Exley, Mark A.

doi:10.1086/378503

Cited by 162 publications

(113 citation statements)

References 24 publications

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“…Interestingly, mice lacking SAP or WASp exhibit impaired iNKTcell thymic development, whereas XIAP-deficient mice have a normal iNKT-cell frequency. A profound deficiency of iNKT-cell numbers and activity was the only immune abnormality found in a girl who developed severe respiratory distress after vaccination with attenuated varicella-zoster virus, a member of the Herpesvirus family [16]. A recent study describes two girls from a consanguineous Turkish family who died after developing severe immune dysregulation and therapy-resistant EBV-positive B-cell proliferation following EBV infection [17].…”

Section: Human Inkt-cell Deficiencies and Viral Infectionsmentioning

confidence: 99%

NKT cells: Friend or foe during viral infections?

Diana

Lehuen

2009

Eur J Immunol

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NKT cells are innate-like T lymphocytes that are found in rodents and primates. They are non-conventional T cells restricted by the CD1d molecule that presents self and exogenous glycolipids. NKT cells are unique in their ability to promptly secrete copious amounts of cytokines such as IFN-c and IL-4. Once activated, NKT cells can provide maturation signals to downstream cells, including DC, NK cells, and lymphocytes, thereby contributing to both innate and acquired immunity. Accordingly, NKT cells can influence a wide array of immune responses, including tumor surveillance, maintenance of self-tolerance and anti-infectious defenses. Studies performed with NKT-cell-deficient mice have shown that these cells are critical for the clearance of various pathogens. During bacterial infections, NKT cells can be activated either indirectly by DC or directly by bacterial lipid antigens presented by CD1d. Although viruses do not contain lipid antigens, NKT cells have also been implicated in antiviral responses. The capacity of NKT cells to regulate viral immune-surveillance, either constitutively or post-activation, makes them an attractive clinical target. In this review, we summarize recent publications dealing with the functions and relevance of NKT cells in the context of viral infections, both in murine models and in humans. (Table 1). Immune evasion by impairing CD1d-mediated antigen presentationSeveral viruses have developed immune-evasion strategies that impair CD1d-mediated antigen presentation, suggesting a role for NKT cells in antiviral responses. Infection by Kaposi sarcomaassociated herpes virus down-regulates cell-surface CD1d expression [6]. This effect is due to two viral modulators of immune recognition proteins, which ubiquitinate the cytoplasmic tail of CD1d and thereby accelerates CD1d endocytosis. HSV type 1 (HSV-1) infection leads to defective CD1d recycling from the endosome to the cell surface, due to its trapping in the late endosomal compartment and resulting in reduced cell-surface expression [7]. Likewise, HIV type 1 (HIV-1) down-regulates CD1d expression by increasing CD1d internalization from the cell [50,56,[57][58][59][60] Eur. Mini-Review

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Section: Human Inkt-cell Deficiencies and Viral Infectionsmentioning

confidence: 99%

NKT cells: Friend or foe during viral infections?

Diana

Lehuen

2009

Eur J Immunol

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“…Varicella Zoster (VZV) is a member of the herpesviridae family (HHV-3) known to affect humans [5]. Depending on age, its presentation varies causing chicken pox in the young and shingles in the elderly.…”

Section: Discussionmentioning

confidence: 99%

Disseminated varicella zoster in an immunocompromised patient: A case report

Kennedy¹,

Dhanoa²,

Frey³

2016

IJCRI

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International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations. In an immunocompromised state, such as in our patient, the presentation can be widespread and more severe. Early diagnosis with polymerase chain reaction (PCR) and treatment with anti-virals and analgesics is a top priority for the patient's well-being and clinical outcome. In our case, early detection and treatment allowed only for a minimal duration of the disseminated virus with prompt recovery and discharge from the hospital. Further investigation of the virus' interaction with medications, such as HAART therapy, that potentially alters the expression of the virus despite vaccination, as some studies suggest, could be beneficial. IJCRI publishes

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“…Intact PBPC were monitored for CD1d-reactivity as previously described for blood and BM-derived NKT cells (10,13,15,20,21). The results showed that PBPC contained readily detectable CD1d-reactive T cells producing high levels of IFN-γ (Figure 2A,B,C).…”

Section: Functionally Cd1d-reactive Nkt Cells In Autologous and Allogmentioning

confidence: 99%

“…Quantitative and qualitative defects in iNKT are predictive of progression in certain autoimmune diseases, and CD1d-reactive NKT can mediate specific types of tolerance, implicating these T cells in immune regulation (14). Human CD1d-reactive NKT have also been shown to have CD1d-specific cytotoxic and anti-viral activities (14,19,20). iNKT IFN-γ is essential for model IL-12-dependent anti-tumor responses and cancer patient iNKT have reversible defects (14,21).…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood progenitor cell product contains Th1-biased noninvariant CD1d-reactive natural killer T cells: Implications for posttransplant survival

Shaulov

Yue

Wang

et al. 2008

Experimental Hematology

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OBJECTIVE-Bone marrow (BM) Th1 populations can contribute to graft-versus-leukemia (GvL) responses. G/GM-CSF-mobilized peripheral blood progenitor cells (PBPC) have become widely accepted alternatives to BM transplantation (BMT). T cells co-expressing NK proteins (NKT) include a CD1d-reactive subset which influence immunity by rapidly producing large amounts of Th1 and/ or Th2 cytokines dependent upon microenvironment and disease. There are two types of CD1d-reactive NKT. "iNKT" express a semi-invariant TCR-α. Other "non-invariant" CD1d-reactive NKT from BM and liver produce large amounts of IL-4 or IFN-γ respectively, and within the intestine can be biased in either direction. Recent data suggests that NKT might contribute to clinical benefits of PBPC.METHODS-To address these issues, we phenotypically and functionally studied PBPC NKT.RESULTS-Similarly to BM, NKT-like cells were common in allogeneic and autologous PBPC, there were relatively few classical iNKT, but high CD1d-reactivity concentrated in NKT fractions. Significantly, PBPC CD1d-reactive cells were relatively Th1-biased and their presence was associated with better prognosis. G-CSF treatment of BM to yield PBPC in vivo as well as in vitro Th2-polarizes conventional T cells and iNKT. However, G-CSF treatment of BM in vitro produced Th1-biased NKT, providing a mechanism for opposite polarization of NKT from BM versus PBPC.CONCLUSIONS-These results suggest distinct Th1 CD1d-reactive NKT cells could stimulate anti-tumor responses from those previously described, which can suppress GvHD.

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Disseminated Varicella Infection Due to the Vaccine Strain of Varicella‐Zoster Virus, in a Patient with a Novel Deficiency in Natural Killer T Cells

Cited by 162 publications

References 24 publications

NKT cells: Friend or foe during viral infections?

NKT cells: Friend or foe during viral infections?

Disseminated varicella zoster in an immunocompromised patient: A case report

Peripheral blood progenitor cell product contains Th1-biased noninvariant CD1d-reactive natural killer T cells: Implications for posttransplant survival

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