Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes - PubMed (original) (raw)

Lutfan Lazuardi et al. Immunology. 2005 Jan.

Abstract

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(+) naive 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-gamma gene rearrangements were used as a marker of clonality. This is a reliable tool to detect not only clonal TCR-gammadelta populations but also TCR-alphabeta 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 naive T cells and the apparent dysregulation of T-cell/B-cell interactions in old age.

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Figures

Figure 1

Figure 1

Immuperoxidase stainings of paraffin-embedded tissue. CD4-positive (a, b) and CD8-positive (c, d) cells in the paracortex area of lymph nodes from young (a, c) and old (b, d) donors; original magnification ×400. CD20-positive cells (e, f) which are predominantly located in follicles in young (e) and old (f) donors; original magnification ×40.

Figure 2

Figure 2

Immunofluorescence stainings of paraffin sections of lymph nodes. Stainings were performed with antibodies to CD3 (green) and CD45RA (red) and were analysed by confocal microscopy. Double-positive cells showed a mixed yellow colour. Lymph nodes from young people (a) contained more CD45RA+ CD3+ cells than lymph nodes from elderly people (b). A follicle which contains CD45RA (red) single-positive B cells is indicated by the white arrow. The red and the green channels of the same region are separately demonstrated in (c) to (f): (c, e) young donor, (d, f) old donor; original magnification ×200.

Figure 3

Figure 3

Restriction fragment length polymorphism analysis showing multiple smearing bands (lane 1) indicating a lack of dominant T-cell clones and a single band (lane 2) indicating the presence of a clonal T-cell population. Examples of lymph node tissue from one young person and from one elderly person are shown.

Figure 4

Figure 4

The box plots show the percentage of CD20-expressing cells (a), the proportion of the size of the germinal centre to the mantle zone area (b) as well as the numbers of IgM-expressing (c) and IgG-expressing (d) cells per mm2 based on age groups as well as the presence or absence of clonal T-cell expansions: A–B, lymph nodes from young people, B–D, lymph nodes from elderly people; A and C without clonal expansion, B and D with clonal expansion.

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