[Show abstract][Hide abstract] ABSTRACT: Alterations in the immune system occur with aging, and these contribute to an increased risk of infection and malignancy. The age-associated changes in T cell immunity range from single cell function to the maintenance of cell populations. We investigated the kinetics of CD4+ T cell activation and proliferation in young and elderly subjects after stimulating their peripheral blood mononuclear cells with anti-CD3 and anti-CD28 antibodies (Abs).
The Journal of the Korean Rheumatism Association 01/2009; 16(4). DOI:10.4078/jkra.2009.16.4.271
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of aging on the IL-7-mediated CD8+ T-cell survival pathway and of IL-7 therapy on T-cell immunity. Cells expressing IL-7 receptor (IL-7R) alphahigh and alphalow were identified in a CD45RA+ effector memory (EM(CD45RA+), CD45RA+CCR7-) CD8+ T-cell subset. Elderly subjects (65 years and older) had an increased frequency of EM(CD45RA+) IL-7Ralphalow) CD8+ T cells, leading to decreased STAT5 phosphorylation and survival responses to IL-7 compared with young subjects (40 years and younger). These EM(CD45RA+) IL-7Ralphalow cells were largely antigen experienced (CD27-CD28-), replicatively senescent (CD57+), and perforinhigh CD8+ T cells that had decreased IL-7Ralpha mRNA, independent of guanine and adenine binding protein alpha (GABPalpha) and growth factor independence-1 (GFI1) expression. In measuring T-cell receptor (TCR) repertoires of EM(CD45RA+) CD8+ T cells, the elderly had a limited repertoire in IL-7Ralphahigh and IL-7Ralphalow cells, whereas the young had a diverse repertoire in IL-7Ralphahigh but not in IL-7Ralphalow cells. These findings suggest that aging affects IL-7Ralpha expression by EM(CD45RA+) CD8+ T cells, leading to impaired signaling and survival responses to IL-7, and that IL-7 therapy may improve the survival of EM(CD45RA+) CD8+ T cells with a diverse TCR repertoire in the young but not in the elderly.
[Show abstract][Hide abstract] ABSTRACT: We investigated age-associated changes in the frequency of CD8+ T cell subsets with different functions. Based on expression of CD45RA and CCR7, naïve (CD45RA+ CCR7+), central memory (CM, CD45RA- CCR7+), effector memory (EM, CD45RA- CCR7-) and effector (CD45RA+ CCR7-) CD8+ T cells were identified in peripheral blood from healthy young (n = 17) and elderly (n = 17) people using flow cytometry. The elderly had a decreased frequency of naïve and an increased frequency of EM and effector CD8+ T cells compared to the young. However, both groups had a similar frequency of CM cells. These findings suggest that age-associated changes in CD8+ T cell subsets occur, which could be a potential explanation for altered CD8+ T cell function in the elderly.
Mechanisms of Ageing and Development 10/2004; 125(9):615-8. DOI:10.1016/j.mad.2004.07.001 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the relationship of memory CD4+ T cells with the evolution of influenza virus-specific CD4+ T cell responses in healthy young and elderly people. Elderly individuals had a similar frequency of CD69+CD4+ T cells producing IFN-gamma and TNF-alpha at 1 wk, but a lower frequency of these CD4+ T cells at 3 mo after influenza vaccination. Although the elderly had a higher frequency of central memory (CM; CCR7+CD45RA-) CD4+ T cells, they had a significantly lower frequency of effector memory (EM; CCR7-CD45RA-) CD4+ T cells, and the frequency of the latter memory CD4+ T cells positively correlated with the frequency of influenza virus-specific CD69+CD4+ T cells producing IFN-gamma at 3 mo. These findings indicate that the elderly have an altered balance of memory CD4+ T cells, which potentially affects long term CD4+ T cell responses to the influenza vaccine. Compared with the young, the elderly had decreased serum IL-7 levels that positively correlated with the frequency of EM cells, which suggests a relation between IL-7 and decreased EM cells. Thus, although the healthy elderly mount a level of CD4+ T cell responses after vaccination comparable to that observed in younger individuals, they fail to maintain or expand these responses. This failure probably stems from the alteration in the frequency of CM and EM CD4+ T cells in the elderly that is related to alteration in IL-7 levels. These findings raise an important clinical question about whether the vaccination strategy in the elderly should be modified to improve cellular immune responses.
The Journal of Immunology 08/2004; 173(1):673-81. DOI:10.4049/jimmunol.173.1.673 · 4.92 Impact Factor