IgE regulation and lymphokine patterns in aging humans

Al-Rayes, Hassan; Pachas, William; Mirza, Nadim; Ahern, Deborah; Geha, Raif S.; Vercelli, Donata

doi:10.1016/0091-6749(92)90136-p

Cited by 45 publications

(23 citation statements)

References 41 publications

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“…Thus, the defect in Th2 cell differentiation appears to be due to intrinsic alterations and not simply a secondary consequence of the imbalance in the production of IL-2, IL-4, or IFN-␥ by aging mouse CD4 ϩ T cells in culture. Our observations are consistent with the results reported by H. al-Rayes et al (52) that IL-4 production is diminished in aged human PBL.…”

Section: Discussionsupporting

confidence: 83%

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

Hasegawa

Miki

Hosokawa

et al. 2006

The Journal of Immunology

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Age-related changes in lymphocytes are most prominent in the T cell compartment. There have been substantial numbers of reports on T cell function in aged mice and humans, such as on the production of Th1 and Th2 cytokines, but the results show considerable variation and contradictions. In the present study, we used 8- to 12-mo-old aging mice and a well-established in vitro Th1/Th2 cell differentiation culture system to identify molecular defects in Th1/Th2 cell differentiation that can be detected in the relatively early stages of aging. The capability to differentiate into Th2 cells is reduced in aging mouse CD4+ T cells. Decreased activation of the ERK MAPK cascade upon TCR stimulation, but normal intracellular-free calcium ion concentration mobilization and normal IL-4-induced STAT6 activation were observed in aging mouse CD4+ T cells. In addition, reduced expression of GATA3 was detected in developing Th2 cells. Chromatin remodeling of the Th2 cytokine gene locus was found to be impaired. Th2-dependent allergic airway inflammation was milder in aging mice compared with in young adult mice. These results suggest that the levels of Th2 cell differentiation and resulting Th2-dependent immune responses, including allergic airway inflammation, decline during aging through defects in the activation of the ERK MAPK cascade, expression of GATA3 protein and GATA3-dependent chromatin remodeling of the Th2 cytokine gene locus. In the present study, we provide the first evidence indicating that a chromatin-remodeling event in T cells is impaired by aging.

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Section: Discussionsupporting

confidence: 83%

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

Hasegawa

Miki

Hosokawa

et al. 2006

The Journal of Immunology

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“…The production of IL-4 by human PBMCs was shown to decrease with age [1], which did not agree with results of the mouse studies [19,32]. These inconsistencies may be due to a difference in the experimental stimuli, the phenotype of the responding cells, organs, or species [29].…”

Section: Discussionmentioning

confidence: 47%

“…The mitogen-activated human PBMCs or total T cells from elderly subjects have produced lower [1,4], similar [1,11] or higher [7] levels of INF-Á as compared with those of young subjects. The production of IL-4 by human PBMCs was shown to decrease with age [1], which did not agree with results of the mouse studies [19,32].…”

Section: Discussionmentioning

confidence: 99%

“…Compared with several murine experiments on this topic [28,34,39], human studies are relatively limited. Moreover, previous human studies focused mainly on the cytokines secreted from mixed cell populations and not on purified cells [1,4,11]. No statement can be made regarding a possible downregulatory activity of certain T cell subsets among the elderly.…”

Section: Introductionmentioning

confidence: 99%

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Age-Associated Changes in Interferon-γ and Interleukin-4 Secretion by Purified Human CD4+ and CD8+ T Cells

et al. 2000

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Aging is associated with a decline in immune function. Interferon-γ (IFN-γ) and interleukin-4 (IL-4), two important immune deviation-related cytokines, are mainly produced by type 1 and type 2 T cells, respectively. To investigate the age-associated changes in the secretion of these two cytokines, 20 elderly and 20 young subjects fulfilling the SENIEUR protocol were enrolled. The ratios of CD4+ to CD8+ T cells were not different between the two age groups. The CD4+ and CD8+ T cells were purified by a magnetic cell sorting system, and then activated by concurrent anti-CD3 and anti-CD28 stimulation. The released cytokines were determined by ELISA. Both the CD4+ and the CD8+ T cells of the elderly individuals secreted a significantly larger amount of IFN-γ after activation. Profound IL-4 production by CD8+ T cells was observed in the older subjects compared with that of the young subjects. These data suggested that age-associated decrease in immunity may be related to an imbalance in the secretion of immune deviation cytokines. The number of IL-4-secreting CD8+ T cells (T cytotoxic 2) rose significantly in the older individuals. Our design also provided a useful way to differentiate the T cell subsets secreting the same cytokine, such as IFN-γ-producing T helper 1 and T cytotoxic 1 cells.

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“…Cytokine imbalance might be one of the underlying factors related to these dysfunctions of immune response during aging. Several studies have demonstrated the changes in cytokine synthesis in the elderly; however, conflicting results remain [1,5]. Thus, the goals of the present study included determining the changes in Th2 immune responses against nematode parasites and revealing the mechanism responsible for age-related modifications.…”

mentioning

confidence: 99%

Th2 Immune Responses and Alternatively Activated Macrophages (AAMacs) in Helminth Infection in Aged Mice

Sugawara

Azuma

Onodera

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. This study aims to understand Th2 immune responses and alternative macrophage activation against nematode parasites in aged mice. Eighteen-month (18 M) and three-month (3 M) old C3H/HeN mice were inoculated with Heligmosomoides polygyrus (Hp) larvae. Real-time PCR analysis indicated that interleukin (IL)-4 and IL-13 gene expression was elevated in both groups after infection, but the expression level was significantly low in 18 M mice. Macrophage phenotype was monitored by measuring arginase-1 gene expression and immunofluorescence staining in small intestine, showing a decrease in the number of alternatively activated macrophages (AAMacs) around worm cysts in 18 M mice. These results suggest that the Th2 immune response in aged mice against a nematode parasite was not sufficiently induced to promote AAMacs.

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IgE regulation and lymphokine patterns in aging humans

Cited by 45 publications

References 41 publications

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

Age-Associated Changes in Interferon-γ and Interleukin-4 Secretion by Purified Human CD4+ and CD8+ T Cells

Th2 Immune Responses and Alternatively Activated Macrophages (AAMacs) in Helminth Infection in Aged Mice

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IgE regulation and lymphokine patterns in aging humans

Cited by 45 publications

References 41 publications

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

Age-Associated Changes in Interferon-&gamma; and Interleukin-4 Secretion by Purified Human CD4&plus; and CD8&plus; T Cells

Th2 Immune Responses and Alternatively Activated Macrophages (AAMacs) in Helminth Infection in Aged Mice

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Age-Associated Changes in Interferon-γ and Interleukin-4 Secretion by Purified Human CD4+ and CD8+ T Cells