From naive to effector ‐ alterations with aging

Linton, Phyllis-Jean; Haynes, Laura; Tsui, Lisa; Zhang, Xiaohong; Swain, Susan L.

doi:10.1111/j.1600-065x.1997.tb01023.x

Cited by 113 publications

(100 citation statements)

References 64 publications

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“…7B). It is not likely that these changes are the result of the age-related shift from naive to memory cells because we found similar age-related declines in active RhoA and increases in active Rac using the pigeon cytochrome c-specific AND mouse strain, in which most of the CD4 T cells remain in a naive stage even late in life (55,56). Studies using transfected cell lines suggest that increases in the activity of Rac are directly linked with a decline in ERM phosphorylation (53).…”

Section: Discussionmentioning

confidence: 53%

Age-Related Defects in Moesin/Ezrin Cytoskeletal Signals in Mouse CD4 T Cells

Garcia

Akha

Miller

2007

The Journal of Immunology

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Cytoskeletal proteins of the ezrin-radixin-moesin (ERM) family contribute to T cell activation in response to Ag, and also to T cell polarization in response to connective tissue matrix proteins and chemokine gradients. Previous work has shown that T cells from aged mice are defective in their ability to develop molecular linkages between surface macromolecules and the underlying cytoskeletal framework, both for proteins that move to the synapse and those that are excluded from the site of T cell-APC interaction. T cells from aged mice also show defective cytoskeletal rearrangements and lamellipodia formation when placed in contact with slides coated with Abs to the TCR/CD3 complex. In this study, we show that old CD4 T cells differ from young CD4 T cells in several aspects of ERM biochemistry, including ERM phosphorylation and ERM associations with CD44, CD43, and EBP50. In addition, CD4 T cells from aged mice show defects in the Rho GTPase activities known to control ERM function.

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Section: Discussionmentioning

confidence: 53%

Age-Related Defects in Moesin/Ezrin Cytoskeletal Signals in Mouse CD4 T Cells

Garcia

Akha

Miller

2007

The Journal of Immunology

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“…However, this is counteracted, in part, by the long-term maintenance of large numbers of memory CD8 + T cells in the secondary lymphoid organs and the progressively increasing capacity of these cells to generate proliferative recall responses (Hogan et al, 2001a;Woodland et al, 2001). Overall, it appears that T cell memory is not only maintained for long periods of time, but is also enhanced in the face of an age related decline in the capacity of the immune system to respond to new pathogens (Linton et al, 1997). Table 1 The numbers of Sendai virus NP Fold increase indicates the fold increase in absolute numbers of Sendai-NP…”

Section: Discussionmentioning

confidence: 97%

Aging and CD8+ T cell immunity to respiratory virus infections

Ely

Roberts

Kohlmeier

et al. 2007

Experimental Gerontology

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The capacity of the immune system to mediate effective immune responses to pathogens declines with age. In the case of immune responses to newly encountered antigens, several studies have demonstrated that this decline reflects both a loss of naïve T cells and changes in the repertoire and function of these cells over time. However, comparatively little is known about the impact of age on established memory T cells pools. Here we discuss age-related changes in memory CD8 + T cell pools elicited by influenza and parainfluenza viruses and the impact of these changes on immunity in general.A large number of studies have documented that increasing age is associated with a progressive decline in the capacity to mount effective immune responses (Burns et al., 1993;Cook et al., 1987;Effros, 2003;Grubeck-Loebenstein and Wick, 2002;Linton and Dorshkind, 2004;McElhaney, 2003;McElhaney, 2005;Miller, 1991;Miller, 1996;Murasko and Jiang, 2005;Nagelkerken et al., 1991;Phair et al., 1978;Wick et al., 2000;Zheng et al., 1997). Aged individuals typically have an impaired capacity to clear infections and also exhibit significant defects in graft rejection, delayed type hypersensitivity, and tumor rejection (Haynes and Eaton, 2005;Miller, 1996;Po et al., 2002). These defects have important clinical consequences for the elderly in terms of susceptibility to infection and poor vaccine efficacy. Recent studies have implicated both the cellular and humoral arms of the immune response in this age-related decline in immune function. For example, studies in animals and humans have shown that aged individuals have a significantly reduced capacity to mount an effective antibody response following infection or vaccination, which is thought to be a consequence of dysfunctional aged CD4 + T cell "help" (High, 2004;Johnson and Cambier, 2004). In addition, involution of the thymus results in a decline in naïve T cell numbers, potentially limiting the breadth and quality of the repertoire of the T cell response (Naylor et al., 2005). However, we still lack a solid understanding of the scope of immune defects or mechanisms underlying the decline in immune efficacy in the elderly.Whereas most studies addressing the impact of aging on immunity have focused on immune responses to newly encountered antigens, relatively little work has addressed the impact of age on pre-existing memory T cell populations. Studies by Kapasi et al using a systemic viral model in mice demonstrated that CD8 + T cell memory remains functional for over a year after its initial generation (Kapasi et al., 2002). This is consistent with human studies suggesting that cellular immunity is relatively long lived (Hammarlund et al., 2003). However, the relative efficacy of the recall of long-term T cell memory (ie. memory that was originally established

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“…The assumption always has been that these markers define Agexperienced T cells. Also, it is well established that there is an overall increase in the number of T cells with "memory" markers and also outgrowth of certain oligoclonal T cell populations during aging (21)(22)(23)(24). Once again, it is generally believed that this is due to Ag-driven expansion of T cells and represents the cumulative sum of the response to pathogens we encounter over a lifetime.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: Naive T Cells Masquerading as Memory Cells

Murali‐Krishna

Ahmed

2000

The Journal of Immunology

428

399

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This study shows that naive CD8 T cells can acquire characteristics of memory T cells in the absence of stimulation with specific Ag simply by the process of homeostatic proliferation under lymphopenic conditions. This Ag-independent T cell differentiation pathway did not result in up-regulation of early activation markers (CD69, CD25, CD71), but expression of several memory markers (CD44, CD122, Ly6C) increased progressively with successive divisions. These markers were then stably expressed, and these cells also became more responsive functionally to specific Ag. Thus, all “memory” phenotype T cells in an individual may not be true Ag-experienced cells and may include naive cells masquerading as memory cells. These findings are specially relevant in cases of disease or treatment-induced lymphopenia such as in HIV-infected individuals or transplant recipients. In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules.

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From naive to effector ‐ alterations with aging

Cited by 113 publications

References 64 publications

Age-Related Defects in Moesin/Ezrin Cytoskeletal Signals in Mouse CD4 T Cells

Age-Related Defects in Moesin/Ezrin Cytoskeletal Signals in Mouse CD4 T Cells

Aging and CD8+ T cell immunity to respiratory virus infections

Cutting Edge: Naive T Cells Masquerading as Memory Cells

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