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Depressive symptoms post hip fracture in older adults are associated with phenotypic and functional alterations in T cells.

Duggal NA, Upton J, Phillips AC, Hampson P, Lord JM - Immun Ageing (2014)

Bottom Line: Ageing is accompanied by reduced immunity, termed immunesenescence.The immune system does not act in isolation and is sensitive to both psychological and physical stress.On examining cytokine production by activated T cells, a significant increase in TNFα (p = .03) and IL6 (p = .04) production was observed in CD4 T cells from hip fracture patients with depressive symptoms compared to healthy controls.

View Article: PubMed Central - PubMed

Affiliation: School of Immunity and Infection, University of Birmingham, Birmingham, B15 2TT UK ; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research and, University of Birmingham, Birmingham, B15 2TT UK.

ABSTRACT

Background: Ageing is accompanied by reduced immunity, termed immunesenescence. The immune system does not act in isolation and is sensitive to both psychological and physical stress. Hip fracture is a common physical stressor in older adults with a high incidence of new onset depression, which relates to poorer prognosis. We therefore set out to examine the possible synergistic effects of physical stress (hip fracture) and psychological stress (depressive symptoms) on the aged immune system.

Results: T cell phenotype and function was assessed in 101 hip fracture patients (81 female) 6 weeks after hip fracture and 43 healthy age-matched controls (26 female). 38 fracture patients had depressive symptoms at 6 weeks. T cell frequency (p = .01) and numbers (p = .003) were both lower in depressed hip fracture patients compared to healthy controls. The frequency of senescent CD28(-ve) (p = .001), CD57(+ve) (p = .001), KLRG1(+ve) (p = .03) CD8 T cells, as well as senescent CD28(-ve) CD4(+ve) (p = .01) and CD57(+ve) CD4(+ve) (p = .003) T cells were higher in depressed hip fracture patients compared with healthy controls and the frequency of CD28(-ve) CD8 T cells was also higher when compared to patients with hip fracture alone (p = .01). Additionally, activated CD69(+ve) (p = .005) and HLADR(+ve) (p < .001) CD8 T cells, were also higher in depressed hip fracture patients compared to healthy controls. On examining cytokine production by activated T cells, a significant increase in TNFα (p = .03) and IL6 (p = .04) production was observed in CD4 T cells from hip fracture patients with depressive symptoms compared to healthy controls.

Conclusions: As none of the patients in the study had a prior history of depression, our data suggest that the development of depressive symptoms in hip fracture patients is associated with altered T cell phenotype and increased pro-inflammatory function which is not seen in patients who do not develop depression after hip fracture. Treating depressive symptoms promptly in hip fracture patients may therefore improve immunity and outcomes in these patients.

No MeSH data available.


Related in: MedlinePlus

Frequency of peripheral senescent and exhausted T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of KLRG1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of KLRG1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). (c) Representative flow cytometry plots showing frequency of PD1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of PD1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). Data are mean ± SEM. *p < .05 and **p < .01.
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Fig3: Frequency of peripheral senescent and exhausted T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of KLRG1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of KLRG1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). (c) Representative flow cytometry plots showing frequency of PD1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of PD1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). Data are mean ± SEM. *p < .05 and **p < .01.

Mentions: Killer cell lectin like receptor G 1(KLRG1) has also been identified as a marker for functional senescence in T cells [34]. On examining KLRG1 expression on T cells [Figure 3a], no significant differences were reported in the frequency of KLRG1+ve CD4 T cells, F (2, 55) = 2.53, p = .09, η2 = .08 between the three groups [Figure 3b]. However, significant differences were seen in the percentage of KLRG1+ve CD8 T cells between our groups, F (2, 55) = 3.91, p = .02, η2 = .12, driven by an increase in hip fracture patients with depressive symptoms compared with healthy controls (p = .03).Figure 3


Depressive symptoms post hip fracture in older adults are associated with phenotypic and functional alterations in T cells.

Duggal NA, Upton J, Phillips AC, Hampson P, Lord JM - Immun Ageing (2014)

Frequency of peripheral senescent and exhausted T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of KLRG1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of KLRG1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). (c) Representative flow cytometry plots showing frequency of PD1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of PD1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). Data are mean ± SEM. *p < .05 and **p < .01.
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Related In: Results  -  Collection

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Fig3: Frequency of peripheral senescent and exhausted T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of KLRG1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of KLRG1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). (c) Representative flow cytometry plots showing frequency of PD1+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of PD1+ve CD4 and CD8 T cells in healthy controls: n = 23 (open bars); hip fracture patients without depression n = 19 (grey bars); and hip fracture patients with depressive symptoms n = 23 (black bars). Data are mean ± SEM. *p < .05 and **p < .01.
Mentions: Killer cell lectin like receptor G 1(KLRG1) has also been identified as a marker for functional senescence in T cells [34]. On examining KLRG1 expression on T cells [Figure 3a], no significant differences were reported in the frequency of KLRG1+ve CD4 T cells, F (2, 55) = 2.53, p = .09, η2 = .08 between the three groups [Figure 3b]. However, significant differences were seen in the percentage of KLRG1+ve CD8 T cells between our groups, F (2, 55) = 3.91, p = .02, η2 = .12, driven by an increase in hip fracture patients with depressive symptoms compared with healthy controls (p = .03).Figure 3

Bottom Line: Ageing is accompanied by reduced immunity, termed immunesenescence.The immune system does not act in isolation and is sensitive to both psychological and physical stress.On examining cytokine production by activated T cells, a significant increase in TNFα (p = .03) and IL6 (p = .04) production was observed in CD4 T cells from hip fracture patients with depressive symptoms compared to healthy controls.

View Article: PubMed Central - PubMed

Affiliation: School of Immunity and Infection, University of Birmingham, Birmingham, B15 2TT UK ; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research and, University of Birmingham, Birmingham, B15 2TT UK.

ABSTRACT

Background: Ageing is accompanied by reduced immunity, termed immunesenescence. The immune system does not act in isolation and is sensitive to both psychological and physical stress. Hip fracture is a common physical stressor in older adults with a high incidence of new onset depression, which relates to poorer prognosis. We therefore set out to examine the possible synergistic effects of physical stress (hip fracture) and psychological stress (depressive symptoms) on the aged immune system.

Results: T cell phenotype and function was assessed in 101 hip fracture patients (81 female) 6 weeks after hip fracture and 43 healthy age-matched controls (26 female). 38 fracture patients had depressive symptoms at 6 weeks. T cell frequency (p = .01) and numbers (p = .003) were both lower in depressed hip fracture patients compared to healthy controls. The frequency of senescent CD28(-ve) (p = .001), CD57(+ve) (p = .001), KLRG1(+ve) (p = .03) CD8 T cells, as well as senescent CD28(-ve) CD4(+ve) (p = .01) and CD57(+ve) CD4(+ve) (p = .003) T cells were higher in depressed hip fracture patients compared with healthy controls and the frequency of CD28(-ve) CD8 T cells was also higher when compared to patients with hip fracture alone (p = .01). Additionally, activated CD69(+ve) (p = .005) and HLADR(+ve) (p < .001) CD8 T cells, were also higher in depressed hip fracture patients compared to healthy controls. On examining cytokine production by activated T cells, a significant increase in TNFα (p = .03) and IL6 (p = .04) production was observed in CD4 T cells from hip fracture patients with depressive symptoms compared to healthy controls.

Conclusions: As none of the patients in the study had a prior history of depression, our data suggest that the development of depressive symptoms in hip fracture patients is associated with altered T cell phenotype and increased pro-inflammatory function which is not seen in patients who do not develop depression after hip fracture. Treating depressive symptoms promptly in hip fracture patients may therefore improve immunity and outcomes in these patients.

No MeSH data available.


Related in: MedlinePlus