Humoral and Cellular CMV Responses in Healthy Donors; Identification of a Frequent Population of CMV-Specific, CD4+ T Cells in Seronegative Donors

Loeth, Nina; Assing, Kristian; Madsen, Hans O.; Vindeløv, Lars L.; Buus, Søren; Stryhn, Anette

doi:10.1371/journal.pone.0031420

Cited by 18 publications

(26 citation statements)

References 43 publications

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“…Additionally, as recently shown, CMV-seronegative individuals can have CMVresponsive T-cells thereby suggesting a former encounter with CMV, and this might also have affected our analyses. 23,24 Finally, our study is the first to show an association between CMV infection and HZ, further causal relations should be studied in other studies.…”

Section: Discussionmentioning

confidence: 62%

Cytomegalovirus seropositivity is associated with herpes zoster

Ogunjimi

Hens

Pebody

et al. 2015

Human Vaccines & Immunotherapeutics

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Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N D 223) in order to compare the results with those from UK population samples (N D 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 D 1741, N2 D 576), USA (N D 5572) and Australia (N D 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMVseroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ.

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Section: Discussionmentioning

confidence: 62%

Cytomegalovirus seropositivity is associated with herpes zoster

Ogunjimi

Hens

Pebody

et al. 2015

Human Vaccines & Immunotherapeutics

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“…as transplant patients and pregnant women, was recently already shown for CMV (66) and had already been shown for various pathogens, such as hepatitis C virus (67). CMV pp65-specific IFN-␥-producing T cells were more frequent than those against VZV IE63, VZV gE, TT, and AdV penton.…”

Section: Fig 4 Comparing Ifn-␥-producing T-cell Percentages (Of Cd3mentioning

confidence: 62%

Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians

Ogunjimi

Smits

Heynderickx

et al. 2014

Clin. Vaccine Immunol.

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jReexposure to viruses is assumed to strengthen humoral and cellular immunity via the secondary immune response. We studied the effects of frequent exposure to viral infectious challenges on immunity. Furthermore, we assessed whether repetitive exposures to varicella-zoster virus (VZV) elicited persistently high immune responses. Blood samples from 11 pediatricians and matched controls were assessed at 3 time points and 1 time point, respectively. Besides the assessment of general immunity by means of measuring T-cell subset percentages, antibody titers and gamma interferon (IFN-␥)/interleukin 2 (IL-2)-producing T-cell percentages against adenovirus type 5 (AdV-5), cytomegalovirus (CMV), tetanus toxin (TT), and VZV were determined. Pediatricians had lower levels of circulating CD4؉ -naive T cells and showed boosting of CD8 ؉ effector memory T cells. Although no effect on humoral immunity was seen, repetitive exposures to VZV induced persistently higher percentages of IFN-␥-positive T cells against all VZV antigens tested (VZV glycoprotein E [gE], VZV intermediate-early protein 62 [IE62], and VZV IE63) than in controls. T cells directed against latency-associated VZV IE63 benefitted the most from natural exogenous boosting. Although no differences in cellular or humoral immunity were found between the pediatricians and controls for AdV-5 or TT, we did find larger immune responses against CMV antigens in pediatricians. Despite the high infectious burden, we detected a robust and diverse immune system in pediatricians. Repetitive exposures to VZV have been shown to induce a stable increased level of VZVspecific cellular but not humoral immunity. Based on our observations, VZV IE63 can be considered a candidate for a zoster vaccine.

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“…CMV‐specific T cells have been previously reported in CMV‐IgG seronegative individuals. Loeth et al [] detected CMV pp65‐reactive Th cells in healthy CMV‐seronegative blood bank donors and Lúcia et al [] showed CMV‐sensitized individuals with protective CMV‐specific memory T and B cells among seronegative kidney transplant recipients. These T cells may have been induced by previous exposure to CMV which was sufficient to activate T cells but failed to mount an humoral immune response.…”

Section: Discussionmentioning

confidence: 99%

Functional impairment of CMV‐reactive cellular immunity during pregnancy

Reuschel

Barabas

Zeman

et al. 2016

Journal of Medical Virology

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Cytomegalovirus (CMV) is the most common congenital viral infection. Mother-to-child transmission can cause severe child disability. Intact CMV-specific cell-mediated immunity (CMI) was shown to prevent uncontrolled replication in healthy individuals. This study aimed to determine whether CMV-specific CMI is impaired in pregnant women, thus potentially increasing the overall risk for active CMV replication and transmission. CMV-specific CMI in peripheral blood of 60 pregnant women was determined using T-Track® CMV for detection of IE-1 and pp65-reactive effector cells by IFN-γ ELISpot, and compared to the CMV-IgG and -IgM serostatus. CMV-specific CMI was detected in 65% of CMV-seropositive pregnant women. Five percent of CMV-IgG seronegative women showed IE-1- but not pp65-reactive cells. The overall number of CMV-reactive cells in pregnant women was significantly lower compared to a matched non-pregnant control group (P < 0.001). No significant difference in CMV-specific CMI was detected in the course of the three trimesters of pregnancy of CMV-IgG seropositive women. Postpartum (median days postnatal = 123), IE-1- and pp65-specific CMI remained significantly lower than in the non-pregnant control group (P < 0.001 and 0.0032, respectively). Functional analysis of CMV-reactive immune cells using T-Track® CMV therefore suggests a systemic down-regulation of CMV-specific CMI in pregnant women. Further studies are needed to investigate whether this may be indicative of a higher susceptibility to CMV reactivation or transmission. J. Med. Virol. 89:324-331, 2017. © 2016 Wiley Periodicals, Inc.

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Humoral and Cellular CMV Responses in Healthy Donors; Identification of a Frequent Population of CMV-Specific, CD4+ T Cells in Seronegative Donors

Cited by 18 publications

References 43 publications

Cytomegalovirus seropositivity is associated with herpes zoster

Cytomegalovirus seropositivity is associated with herpes zoster

Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians

Functional impairment of CMV‐reactive cellular immunity during pregnancy

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