Age‐related loss of naïve T cells and dysregulation of T‐cell/B‐cell interactions in human lymph nodes

Abstract

Summary In this study we analysed the effects of age on T and B lymphocytes in human lymph nodes by comparing lymphocyte subsets in paraffin sections from lymph node tissue taken from healthy young and elderly people. We demonstrate that the relative number of CD8+ T cells decreases with age but that the relative number of CD4+ T cells does not. There is also a very pronounced age‐dependent loss of CD45RA+ naïve T cells. The number and size of follicles and the relative number of CD20+ B cells are similar in young and elderly donors. For polymerase chain reaction analysis of the T‐cell receptor (TCR) repertoire the TCR‐γ gene rearrangements were used as a marker of clonality. This is a reliable tool to detect not only clonal TCR‐γδ populations but also TCR‐αβ populations. Young donors with clonal T‐cell expansions in their lymph node tissue do, however, have a higher number of CD20+ B cells, a higher relative size of germinal centres compared to the follicle mantles and a higher number of immunoglobulin M‐expressing cells than young donors without evidence of clonal T‐cell expansions. Corresponding changes are not observed in elderly donors with clonal T‐cell expansions in their lymph node tissue. In summary our findings demonstrate characteristic effects of aging on human lymph node tissue, the most striking feature being the depletion of naïve T cells and the apparent dysregulation of T‐cell/B‐cell interactions in old age.

Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients

“…Moreover, in recent years, it has been proposed that defective immune surveillance for EBV may develop late in life and be associated with the development of EBV positive B-cell lymphoproliferative disorder. 47 This defective immune surveillance for EBV is associated with immunological deterioration as a result of aging process, 3,[48][49][50] and explains the correlation between an increased incidence of this lymphoma type together with the increased age of the patients found in the Eastern series. Surprisingly, we did not observe major differences linked with age of the relative numbers of any T-cell population analyzed (Supporting Information Fig.…”

Mouse CMV infection delays antibody class switch upon an unrelated virus challenge

“…Humoral immunity is also affected by aging, because the ability to mount robust humoral immunity upon infection or vaccination diminishes in aging hosts (Hakim and Gress, 2007;Lazuardi et al, 2005). CMV seroposositive hosts showed weaker antibody responses to influenza in some (Moro-Garcia et al, 2012;Trzonkowski et al, 2003), but not all studies (den Elzen et al, 2011), and this weak response correlated to an increase of terminally differentiated CD4 T-cells (Derhovanessian et al, 2013), arguing that CMV may impair both the cellular and the humoral branch of the adaptive immune system.…”

Cardiovascular exercise intervention improves the primary antibody response to keyhole limpet hemocyanin (KLH) in previously sedentary older adults

“…Adequate responses to vaccination are important in protecting older adults from infectious diseases such as influenza virus, pneumococcal disease, varicella zoster virus, and Clostridium tetani. Cellular changes associated with the age-related loss of vaccine efficacy include; deficits in antigen presentation by dendritic cells (Agrawal et al, 2007), thymic involution and decreasing numbers of naïve CD4+ T cells (Goronzy & Weyand, 2005), and increasing numbers of both memory CD4+ and CD8+ T cells and memory B cells (Effros, 2007;Lazuardi et al, 2005;Saurwein-Teissl et al, 2002). Interestingly, several independent studies have demonstrated that high proportions of CD8+ T lymphocytes that lack expression of the important costimulatory molecule CD28 predict poor vaccine responses (Vallejo, 2005).…”