Age-associated Epstein–Barr virus-specific T cell responses in seropositive healthy adults

Abstract

SummaryEpstein-Barr virus (EBV) is present in 95% of the world's adult population. The immune response participates in immune vigilance and persistent infection control, and this condition is maintained by both a good quality (functionality) and quantity of specific T cells throughout life. In the present study, we evaluated EBV-specific CD4 + and CD8 + T lymphocyte responses in seropositive healthy individuals younger and older than 50 years of age. The assessment comprised the frequency, phenotype, functionality and clonotypic distribution of T lymphocytes. We found that in both age groups a similar EBV-specific T cell response was found, with overlapping numbers of tumour necrosis factor (TNF)-α + T lymphocytes (CD4 + and CD8 + ) within the memory and effector cell compartments, in addition to monofunctional and multi-functional T cells producing interleukin (IL)-2 and/or interferon (IFN)-γ. However, individuals aged more than 50 years showed significantly higher frequencies of IL-2-producing CD4 + T lymphocytes in association with greater production of soluble IFN-γ, TNF-α and IL-6 than subjects younger than 50 years. A polyclonal T cell receptor (TCR)-variable beta region (Vβ) repertoire exists in both age groups under basal conditions and in response to EBV; the major TCR families found in TNF-α + /CD4 + T lymphocytes were Vβ1, Vβ2, Vβ17 and Vβ22 in both age groups, and the major TCR family in TNF-α + /CD8 + T cells was Vβ13·1 for individuals younger than 50 years and Vβ9 for individuals aged more than 50 years. Our findings suggest that the EBV-specific T cell response (using a polyclonal stimulation model) is distributed throughout several T cell differentiation compartments in an age-independent manner and includes both monofunctional and multi-functional T lymphocytes.

Epstein–Barr virus-specific CD8+ T lymphocytes from diffuse large B cell lymphoma patients are functionally impaired

“…In addition, a polyclonal and highly overlapping TCR‐Vβ repertoire of both CD4 + and CD8 + T lymphocytes was found in both age groups, although greater frequencies of Vβ13·1 and Vβ9 were found in younger and older subjects, respectively, together with a proinflammatory environment that seemed to be more evident among older subjects. Taken together, these results suggested that a common selection of TCR‐Vβ families that changes over the years could be relevant in controlling EBV infection in healthy seropositive individuals .…”

“…d). Notably, CD8 + /TNF‐α + T lymphocytes of the healthy controls and DLBCL patients showed interindividual variability in the distribution within the effector/memory compartment, suggesting different immunological backgrounds for each individual .…”

“…However, previous studies on human leucocyte antigen (HLA)‐B8‐positive IM patients, showing the persistence of dominant specific clonotypes from acute infection into memory against immunodominant latent cycle epitope FLR, suggest that the composition of the FLR‐specific repertoire does not vary dramatically over time . In fact, distinct patterns of CD8 + T cell differentiation and expansion may be primed by different routes of antigen exposure or particular homeostatic environments occurring in different viral infections, as well as whether the cells respond to epitopes from lytic or latent EBV proteins or a whole lysate . These reasons could explain the differences observed in our results compared to previous studies in which peptides are used to evaluate the specific immune response to EBV.…”

Loss of T-Cell Multifunctionality and TCR-Vβ Repertoire Against Epstein-Barr Virus Is Associated With Worse Prognosis and Clinical Parameters in HIV+ Patients

“…Relevant clinical characteristics of patients are summarized in Table 1 . Sixteen patients were at stage 1, 20 were at stage 2 and 20 were at stage 3; 6 of 62 patients had B-cell non-Hodgkin lymphoma ( 19 ). This study was approved by the Research and Ethics Committee of the Faculty of Sciences of the Pontificia Universidad Javeriana (May 8th, 2014 session) and the Committee of Research and Ethics of the Faculty of Medicine of the Hospital Universitario San Ignacio (Ref.…”

“…Intracellular cytokines were determined by adding 1 μg/mL Brefeldin A (BFA; BD Biosciences) to cultures at the second hour of the 6 h incubation period. As positive controls, 1 × 10 6 leukocytes were cultured with a polyclonal stimulus (10 ng/mL PMA and 1 μg/mL ionomycin) for 4 h at 37°C and 5% CO 2 atmosphere ( 13 , 19 ). Then, cells were stained with the following fluorochrome-conjugated anti-human mAbs: anti-CD3-PECy7 (clone SK7; BD Pharmingen), anti-CD4-PerCP (clone HP2/6; Immunostep SL), and anti-CD8-APC-Cy7 (SK1; BD Pharmingen) for 15 min at room temperature and in the dark.…”