Time course characteristics of human herpesvirus 6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum

Kumagai, Toshiko; Yoshikawa, Tetsushi; Yoshida, Minoru; Okui, Toyo; Ihira, Masaru; Nagata, Nobuyuki; Yano, Shoki; Shiraki, Kimíyasu; Yamada, Masao; Ichihara, Kiyoshi; Asano, Yoshizo

doi:10.1002/jmv.20625

Cited by 15 publications

(8 citation statements)

References 31 publications

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“…Human herpesvirus-6 reactivation events are thought to occur periodically in healthy carriers and to be subclinical due to intact immune surveillance. Natural killer cells appear to have anti-HHV-6 function ( 6 ), as implied by their activity in the acute febrile phase of primary infection ( 7 , 8 ) and cytotoxicity against HHV-6-infected cells ( 9 ) in an interleukin-15-dependent manner ( 10 ). There is little evidence that antibody deficiency disorders increase risk of complications from infection by these viruses ( 11 ), and B cell deficiency does not increase lethality of murine roseolovirus (MRV), a betaherpesvirus related to HHV-6, in neonatal mice ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

2018

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Human herpesvirus (HHV) 6 is thought to remain clinically latent in most individuals after primary infection and to reactivate to cause disease in persons with severe immunosuppression. In allogeneic hematopoietic stem cell transplant recipients, reactivation of HHV-6 species B is a considerable cause of morbidity and mortality. HHV-6B reactivation is the most frequent cause of infectious meningoencephalitis in this setting and has been associated with a variety of other complications such as graft rejection and acute graft versus host disease. This has inspired efforts to develop HHV-6-targeted immunotherapies. Basic knowledge of HHV-6-specific adaptive immunity is crucial for these endeavors, but remains incomplete. Many studies have focused on specific HHV-6 antigens extrapolated from research on human cytomegalovirus, a genetically related betaherpesvirus. Challenges to the study of HHV-6-specific T-cell immunity include the very low frequency of HHV-6-specific memory T cells in chronically infected humans, the large genome size of HHV-6, and the lack of an animal model. This review will focus on emerging techniques and methodological improvements that are beginning to overcome these barriers. Population-prevalent antigens are now becoming clear for the CD4+ T-cell response, while definition and ranking of CD8+ T-cell antigens and epitopes is at an earlier stage. This review will discuss current knowledge of the T-cell response to HHV-6, new research approaches, and translation to clinical practice.

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Section: Introductionmentioning

confidence: 99%

“…Compared to other herpesviruses, HHV-6-specific cell-mediated response is delayed in primary infection ( 8 ). This correlates with, and could be mechanistically related to, HHV-6 lymphotropism ( 13 – 15 ), since activated HHV-6-responsive T cells may be differentially susceptible to destructive viral infection.…”

Section: Introductionmentioning

confidence: 99%

Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

2018

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“…Subsequent studies using peripheral blood mononuclear cells (PBMCs) have demonstrated T cell responses by both CD4 ϩ and CD8 ϩ T cells (24,40,77). However, HHV-6-specific T cell clones and T cell lines (TCLs) have been established only for CD4 ϩ T cells (40,42,69,80,81,87). The fine specificity of the T cell response to HHV-6 is largely unexplored.…”

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confidence: 99%

Human CD4⁺T Cell Response to Human Herpesvirus 6

Nastke

Becerra

Yin

et al. 2012

J Virol

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Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell lines generated from healthy donors. CD4؉ T cells responding to HHV-6 in peripheral blood were observed at frequencies below 0.1% of total T cells but could be expanded easily in vitro. Analysis of cytokines in supernatants of PBMC and T cell cultures challenged with HHV-6 preparations indicated that gamma interferon (IFN-␥) and interleukin-10 (IL-10) were appropriate markers of the HHV-6 cellular response. Eleven CD4 ؉ T cell epitopes, all but one derived from abundant virion components, were identified. The response was highly cross-reactive between HHV-6A and HHV-6B variants. Seven of the CD4 ؉ T cell epitopes do not share significant homologies with other known human pathogens, including the closely related human viruses human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers generated with these epitopes were able to detect HHV-6-specific T cell populations. These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses.

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“…Acute HHV-6 infection stimulates cellular immunoregulatory mediators (IL-1, INF-α, INF-γ, TNF-α) and natural killer (NK) cell cytotoxicity (1,(26)(27)(28)(29). Monocyte and monocyte-derived dendritic cells are targets of HHV-6 in the pathogenesis and immunosuppressive effect during acute infection (30,31).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Roseola Infantum Cases in Terms of Demographic Properties and Laboratory Values

Bıçakçı¹,

Arvas²,

Biçer³

et al. 2017

J Pediatr Inf

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Objective: To share our experince from demographic and labaratory results of 46 patients who applied to our policlinic with complaints of fever and rash and diagnosed as roseola infantum between 2012-2016. Material and Methods: Labaratory and demographic findings of 41 patients who diagnosed as roseola infantum clinically had been evaluated. Roseala infantum cases were diagnosed as 10 mo old infant with high temperature over three days and nontoxic maculopapuller rash on the trunk and after making differential diagnosis of other diseases that courses with skin rash and high body temperature. Neutrophil counts between 0-500, 500-1000 and 1000-1500 were accepted as high, medium and low, respectively. Results: 25 of the patients were female (54.3%), 21 of them were male (45.7%), mean age was 11.5 ± 7.02 (3-36 months) and peak age of onset was 9-11 months. 76% of patients were (35/46) under one years of age. Disease was seen all year round but it was seen least at September and October and was seen mostly at December. Mean labaratory leves were found as: Hb 11.

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Time course characteristics of human herpesvirus 6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum

Cited by 15 publications

References 31 publications

Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

Human CD4⁺T Cell Response to Human Herpesvirus 6

Evaluation of Roseola Infantum Cases in Terms of Demographic Properties and Laboratory Values

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Time course characteristics of human herpesvirus 6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum

Cited by 15 publications

References 31 publications

Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

Human CD4+T Cell Response to Human Herpesvirus 6

Evaluation of Roseola Infantum Cases in Terms of Demographic Properties and Laboratory Values

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Human CD4⁺T Cell Response to Human Herpesvirus 6