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Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.

Jayasooriya S, de Silva TI, Njie-jobe J, Sanyang C, Leese AM, Bell AI, McAulay KA, Yanchun P, Long HM, Dong T, Whittle HC, Rickinson AB, Rowland-Jones SL, Hislop AD, Flanagan KL - PLoS Pathog. (2015)

Bottom Line: In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells.That response was culled and the cells lost activation markers over time, just as seen in AIM.However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Laboratories, Fajara, The Gambia; School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.

ABSTRACT
Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14-18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms.

No MeSH data available.


Related in: MedlinePlus

Size of lymphocyte populations in the blood of Gambian children and AIM patients.Absolute numbers of selected T and B-cell subsets were measured from EBV non-infected (IgM-IgG-), established infection (IgM-IgG+) or recently infected (IgM+IgG+/-) Gambian children and UK donors with AIM. Counts were based on full blood count analysis to obtain lymphocyte numbers and flow cytometric analysis to identify population frequencies. No significant differences in subset counts were observed between different donor groups in Gambian children. UK IM donors had a significantly greater proportion CD8+ T-cells. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001.
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ppat.1004746.g003: Size of lymphocyte populations in the blood of Gambian children and AIM patients.Absolute numbers of selected T and B-cell subsets were measured from EBV non-infected (IgM-IgG-), established infection (IgM-IgG+) or recently infected (IgM+IgG+/-) Gambian children and UK donors with AIM. Counts were based on full blood count analysis to obtain lymphocyte numbers and flow cytometric analysis to identify population frequencies. No significant differences in subset counts were observed between different donor groups in Gambian children. UK IM donors had a significantly greater proportion CD8+ T-cells. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001.

Mentions: Primary symptomatic infection with EBV is associated with dramatic expansions in the frequency and absolute number of lymphocyte subsets, especially CD8+ lymphocytes [6]. Evidence of disruptions to the lymphocyte compartments of the three groups of children (IgM− IgG−, IgM− IgG+ or IgM+ IgG+/−) were studied by determining absolute numbers of lymphocytes within the CD3, CD4, CD8 and CD19 subsets. Fig. 3 shows results of absolute cell counts and, for comparison, counts of equivalent subsets from six Caucasian AIM patients. Dramatic expansions of the CD3+ and CD8+ (but not CD4+) T-cell numbers and a contraction of B cell numbers were seen in AIM patient samples. However, no obvious or significant expansion of lymphocyte subsets was observed when comparing uninfected children with the two EBV-infected groups. Furthermore, no significant changes in the CD4:CD8 ratios were observed in PBMCs from a subset of 14 children over the six month study period (p = 0.76, S2 Fig). This indicated that there was little disruption to peripheral lymphocyte subsets in children at these different stages of asymptomatic EBV infection.


Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.

Jayasooriya S, de Silva TI, Njie-jobe J, Sanyang C, Leese AM, Bell AI, McAulay KA, Yanchun P, Long HM, Dong T, Whittle HC, Rickinson AB, Rowland-Jones SL, Hislop AD, Flanagan KL - PLoS Pathog. (2015)

Size of lymphocyte populations in the blood of Gambian children and AIM patients.Absolute numbers of selected T and B-cell subsets were measured from EBV non-infected (IgM-IgG-), established infection (IgM-IgG+) or recently infected (IgM+IgG+/-) Gambian children and UK donors with AIM. Counts were based on full blood count analysis to obtain lymphocyte numbers and flow cytometric analysis to identify population frequencies. No significant differences in subset counts were observed between different donor groups in Gambian children. UK IM donors had a significantly greater proportion CD8+ T-cells. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376400&req=5

ppat.1004746.g003: Size of lymphocyte populations in the blood of Gambian children and AIM patients.Absolute numbers of selected T and B-cell subsets were measured from EBV non-infected (IgM-IgG-), established infection (IgM-IgG+) or recently infected (IgM+IgG+/-) Gambian children and UK donors with AIM. Counts were based on full blood count analysis to obtain lymphocyte numbers and flow cytometric analysis to identify population frequencies. No significant differences in subset counts were observed between different donor groups in Gambian children. UK IM donors had a significantly greater proportion CD8+ T-cells. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001.
Mentions: Primary symptomatic infection with EBV is associated with dramatic expansions in the frequency and absolute number of lymphocyte subsets, especially CD8+ lymphocytes [6]. Evidence of disruptions to the lymphocyte compartments of the three groups of children (IgM− IgG−, IgM− IgG+ or IgM+ IgG+/−) were studied by determining absolute numbers of lymphocytes within the CD3, CD4, CD8 and CD19 subsets. Fig. 3 shows results of absolute cell counts and, for comparison, counts of equivalent subsets from six Caucasian AIM patients. Dramatic expansions of the CD3+ and CD8+ (but not CD4+) T-cell numbers and a contraction of B cell numbers were seen in AIM patient samples. However, no obvious or significant expansion of lymphocyte subsets was observed when comparing uninfected children with the two EBV-infected groups. Furthermore, no significant changes in the CD4:CD8 ratios were observed in PBMCs from a subset of 14 children over the six month study period (p = 0.76, S2 Fig). This indicated that there was little disruption to peripheral lymphocyte subsets in children at these different stages of asymptomatic EBV infection.

Bottom Line: In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells.That response was culled and the cells lost activation markers over time, just as seen in AIM.However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Laboratories, Fajara, The Gambia; School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.

ABSTRACT
Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14-18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms.

No MeSH data available.


Related in: MedlinePlus