Alterations in the human immune response to the hepatitis B vaccine among the elderly

Cook, J.M.; Gualde, N.; Hessel, Luc; Mounier, M; Michel, Jean‐Pierre; Denis, F.; Ratinaud, Marie‐Hélène

doi:10.1016/0008-8749(87)90294-2

Cited by 69 publications

(39 citation statements)

References 25 publications

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“…As a consequence of diminished immune function, humans older than 65 y are more susceptible to infections (e.g., influenza, tuberculosis) (2,3), have higher reactivation rates of persistent viruses (e.g., varicellazoster virus) (4), and respond less effectively to vaccination (5)(6)(7)(8)(9). The inability of elderly populations to rapidly control or eliminate infections not only increases their risk for serious sequalae of the primary infections, but also can contribute to a decline in health on multiple levels caused by events including increased risk of secondary infections and/or cardiovascular complications (10).…”

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confidence: 99%

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Decman

Laidlaw

DiMenna

et al. 2010

The Journal of Immunology

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Although previous studies have demonstrated delayed viral clearance and blunted effector T cell responses in aged mice during infection, memory CD8 T cells and especially secondary responses have received less attention. In this study, we show that modest differences in the number of memory CD8 T cells formed in aged versus young animals were associated with altered memory CD8 T cell differentiation. Aged immune mice had increased morbidity and mortality upon secondary viral challenge, suggesting changes in T cell immunity. Indeed, virus-specific memory CD8 T cells from aged mice showed substantially reduced proliferative expansion upon secondary infection using multiple challenge models. In addition, this defect in recall capacity of aged memory CD8 T cells was cell-intrinsic and persisted upon adoptive transfer into young mice. Thus, the poor proliferative potential of memory T cells and altered memory CD8 T cell differentiation could underlie age-related defects in antiviral immunity.

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confidence: 99%

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Decman

Laidlaw

DiMenna

et al. 2010

The Journal of Immunology

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“…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).…”

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confidence: 99%

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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“…However, the efficacy of vaccination of the elderly is undermined because of age-related defects in the immune system. This has been observed for a variety of vaccines including Streptococcus pneumoniae, influenza, hepatitis, and tetanus (1)(2)(3)(4) and is thought to be the result of a compromised immune response. Importantly, the cognate helper functions of CD4 T cells are particularly defective in the aged (5).…”

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confidence: 99%

“…This leads to a greater incidence and severity of infectious disease and is the reason that the elderly are a major population targeted for vaccination (1)(2)(3)(4). However, the efficacy of vaccination of the elderly is undermined because of age-related defects in the immune system.…”

mentioning

confidence: 99%

Inflammatory Cytokines Overcome Age-Related Defects in CD4 T Cell Responses In Vivo

Haynes

Eaton

Burns

et al. 2004

The Journal of Immunology

156

148

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Age-related decreases in immune function are thought to contribute to the reduced efficacy of vaccinations seen in elderly populations. Our previous in vitro studies demonstrated that naive CD4 T cells from aged TCR-transgenic mice proliferate less than young cells and generate poorly functioning effectors due to decreased IL-2 production. In this current study, we show that this age-related defect in CD4 T cell response also occurs in vivo and that it is correlated with reduced NF-κB activation. After transfer to young hosts, CD4 T cells from aged transgenic mice proliferate less and produce reduced levels of IL-2 upon immunization with Ag and alum. Introducing a combination of the inflammatory cytokines TNF-α, IL-1, and IL-6, or the use of an adjuvant such as CFA that induces these cytokines, markedly enhanced responses of these aged CD4 T cells, so that they proliferated and produced IL-2 similar to young cells. This enhancement is correlated with the enhanced activation of the transcription factor NF-κB in aged cells. We suggest that induction of inflammatory cytokines via adjuvants may enhance the efficacy of vaccinations in elderly populations.

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Alterations in the human immune response to the hepatitis B vaccine among the elderly

Cited by 69 publications

References 25 publications

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Aging and CD8+ T cell immunity to respiratory virus infections

Inflammatory Cytokines Overcome Age-Related Defects in CD4 T Cell Responses In Vivo

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