Differential age-change in the numbers of CD4+CD45RA+ DC4+CD29+ T cell subsets in human peripheral blood

Utsuyama, Masanori; Hirokawa, Katsuíku; Kurashima, Chieri; Fukayama, Makiko; Igarashi, Takashi; Suzuki, Kenshi; Hashimoto, Wataru; Sato, Kazuto

doi:10.1016/0047-6374(92)90016-7

Cited by 229 publications

(122 citation statements)

References 19 publications

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“…The percentage of positive cells for all three antibodies correlated well between viable cells and flow-FISH processed cells. Note that the percentage CD45RA positive cells and CD20 positive cells decreased with age whereas the percentage CD57 positive cells increased with age as was previously described (25). The results of Multicolor flow-FISH using these antibodies to measure the telomere length in diverse leukocyte subsets within one sample are shown in Figure 2.…”

Section: In Situ Hybridization and Immunostainingsupporting

confidence: 67%

Telomere length measurements in leukocyte subsets by automated multicolor flow‐FISH

2003

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Background:Telomeres are essential protein-DNA structures at the end of chromosomes which are implicated in genome stability and cell replication. The average length of telomere repeats can be measured by in situ hybridization and flow cytometry [flow-FISH]. Such telomere length values reflect telomere shortening (resulting from cell divisions, oxidative damage and other causes) and telomere elongation (mainly resulting from telomerase activity) of the chromosome-specific telomere length inherited in the gametes. Here we report improvements in flow-FISH methodology that enable measurements of telomere length in subsets of human nucleated blood cells. Methods and Results:In order to measure the telomere length in granulocytes, naive T cells, memory T cells, B cells and natural killer (NK)/NKT cells within a blood sample, we combined flow-FISH with antibody-staining

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Section: In Situ Hybridization and Immunostainingsupporting

confidence: 67%

Telomere length measurements in leukocyte subsets by automated multicolor flow‐FISH

2003

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“…Apparently, a considerable amount of post-thymically proliferated naive CD4 + T cells within the naive CD4 + T cell pool is present already at younger ages and their numbers are rather independent of thymic activity. As their relative frequency increases with age, they play a central role in adaptive immunity of aged individuals as they provide sufficient numbers of naive CD4 + T cells in the presence of a drastically reduced thymic function and contribute to the rather slow decline in naive T cell numbers in the elderly [24,25]. However, this is traded for the drawback of a reduced TCR repertoire diversity in CD31 -central naive CD4 + T cells as demonstrated by a reduction in the number of peaks and the loss of Gaussian distribution in the CDR3 spectratyping analysis.…”

Section: Discussionmentioning

confidence: 99%

Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults

et al. 2005

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In spite of thymic involution early in life, the numbers of naive CD4 + T cells only slowly decline in ageing humans implying peripheral post-thymic naive CD4 + T cell expansion. This proliferation may compensate for continuous activation and death of naive CD4 + T cells but may also have negative consequences for protective immunity. Here we show that naive CD4 + T cells that have proliferated in the periphery are characterized by a highly restricted oligoclonal TCR repertoire. Additionally these cells, which constitute the majority of naive CD4 + T cells in the elderly, display signatures of recent TCR engagement. Our results demonstrate for the first time that peripheral post-thymic proliferation of naive CD4 + T cells in healthy human individuals causes a significant contraction of the peripheral TCR repertoire. This age-dependent deterioration of CD4 + T cell immunity could entail ageing-associated autoimmunity, increased susceptibility to infection or cancer and decreased efficiency of vaccination.

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“…Although we did not observe any age-related alteration of telomerase induction in lymphocyte subsets after short term stimulation, it is not clear whether or not sustained induction of telomerase activity changes with age. Previous reports have shown an age-associated increase of activationinduced apoptosis (40 -42) and changes in subset composition (3,43) and in immune functions (1). It is possible that some of these age-related factors may affect the sustained expression of telomerase in lymphocytes during long term culture or in vivo.…”

Section: Figurementioning

confidence: 99%

Lineage-Specific Telomere Shortening and Unaltered Capacity for Telomerase Expression in Human T and B Lymphocytes with Age

Son

Murray

Yanovski

et al. 2000

The Journal of Immunology

185

147

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Age effects on telomere length and telomerase expression in peripheral blood lymphocytes were analyzed from 121 normal individuals age newborn to 94 years and revealed several new findings. 1) Telomere shortening was observed in CD4+ and CD8+ T and B cells with age. However, the rate of telomere loss was significantly different in these populations, 35 ± 8, 26 ± 7, and 19 ± 7 bp/year for CD4+ and CD8+ T and B cells, respectively. In addition, CD4+ T cells had the longest average telomeres at all ages, followed by B cells, with CD8+ T cell telomeres the shortest, suggesting that these lymphocyte populations may have different replicative histories in vivo. 2) Telomerase activity in freshly isolated T and B cells was indistinguishably low to undetectable at all ages but was markedly increased after Ag and costimulatory receptors mediated stimulation in vitro. Furthermore, age did not alter the magnitude of telomerase activity induced after stimulation of T or B lymphocytes through Ag and costimulatory receptors or in response to PMA plus ionomycin treatment. 3) The levels of telomerase activity induced by in vitro stimulation varied among individual donors but were highly correlated with the outcome of telomere length change in CD4+ T cells after Ag receptor-mediated activation. Together, these results indicate that rates of age-associated loss of telomere length in vivo in peripheral blood lymphocytes is specific to T and B cell subsets and that age does not significantly alter the capacity for telomerase induction in lymphocytes.

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Differential age-change in the numbers of CD4+CD45RA+ DC4+CD29+ T cell subsets in human peripheral blood

Cited by 229 publications

References 19 publications

Telomere length measurements in leukocyte subsets by automated multicolor flow‐FISH

Telomere length measurements in leukocyte subsets by automated multicolor flow‐FISH

Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults

Lineage-Specific Telomere Shortening and Unaltered Capacity for Telomerase Expression in Human T and B Lymphocytes with Age

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