T cells and aging update February 1999

Abstract

T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

Activation of Thymic Regeneration in Mice and Humans following Androgen Blockade

“…Castration restored the responsiveness to HSV to levels equivalent to those seen in young mice, possibly relating to a restoration of the CD4:CD8 T cell ratio in the resting lymph node population (data not shown). It would be of interest to assess the function of APC in this model because these have been shown to be defective in aged mice (53), are vital for proper viral responsiveness (50), and are able to be modulated by sex steroids (54).…”

Aging affects the proportions of T and B cells in a group of elderly men in a developing country—a pilot study from Pakistan

“…In the process of aging over time, more memory cells are generated; the body has only a limited capacity of cells it can sustain and the immune system favors memory over naïve cells, which is the basis of adaptive immunity. These age-associated alterations and their consequences have been reviewed elsewhere by us Larbi et al 2008;Pawelec et al 1999) and many others. The present study found a tendency towards the presence of lower percentages of CD4+ cells and reciprocally, highly significantly more CD8+ (p < 0.0001) cells in the elderly compared to the young in a rural population of Pakistani men.…”

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

“…The healthy elderly have an increased proportion of memory CD4 ϩ and CD8 ϩ T cells expressing the surface marker CD45RO and a decreased proportion of naive T cells expressing CD45RA (2)(3)(4), although the absolute and relative numbers of CD4 ϩ and CD8 ϩ T cells appear to remain unchanged with aging (1). Elderly individuals have decreased T cell proliferative responses to mitogens in vitro and less IL-2 secretion from Ag-stimulated T cells compared with young people (1,5,6), perhaps related to decreased expression of CD28, a costimulatory molecule critical for T cell activation (7,8). Studies of T cell cytokine synthesis in the elderly have yielded conflicting data.…”