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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 T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of CD28+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of CD28-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 (black bars): n = 23. Data are mean ± SEM. *p < .05 and **p < .01. (c) Representative flow cytometry plots showing frequency of CD57+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of CD57+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 (black bars): n = 23.
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Fig2: Frequency of peripheral senescent T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of CD28+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of CD28-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 (black bars): n = 23. Data are mean ± SEM. *p < .05 and **p < .01. (c) Representative flow cytometry plots showing frequency of CD57+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of CD57+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 (black bars): n = 23.

Mentions: CD28 is a co-stimulatory molecule involved in T cell activation which is lost as T cells progress towards senescence. PBMCs were stained with an anti-CD28 antibody to identify CD28-ve and CD28+ve cells [Figure 2a]. On examining the frequency of circulating CD28-ve CD4 T cells, we found significant differences between the three groups, F (2, 62) = 5.26, p = .008, η2 = .14, driven by a significant increase in the percentage of CD28-ve CD4 T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .01) and hip fracture patients without depressive symptoms (p = .04) [Figure 2b]. Similarly, differences in the frequency of circulating CD28-ve CD8 T cells were found between the three groups, F (2, 62) = 8.30, p = .001, η2 = .21, driven by a significant increase in the percentage of CD28-ve CD8 T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .001) and hip fracture patients without depressive symptoms (p = .01) [Figure 2b]. When the above analyses were repeated with adjustment for age, sex and BMI, the results remained significant (data not shown).Figure 2


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 T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of CD28+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of CD28-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 (black bars): n = 23. Data are mean ± SEM. *p < .05 and **p < .01. (c) Representative flow cytometry plots showing frequency of CD57+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of CD57+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 (black bars): n = 23.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307912&req=5

Fig2: Frequency of peripheral senescent T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Representative flow cytometry plots showing frequency of CD28+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (b) The percentage of CD28-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 (black bars): n = 23. Data are mean ± SEM. *p < .05 and **p < .01. (c) Representative flow cytometry plots showing frequency of CD57+ve CD8 T cells in a healthy control, hip fracture and a hip fracture patient with depressive symptoms. (d) The percentage of CD57+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 (black bars): n = 23.
Mentions: CD28 is a co-stimulatory molecule involved in T cell activation which is lost as T cells progress towards senescence. PBMCs were stained with an anti-CD28 antibody to identify CD28-ve and CD28+ve cells [Figure 2a]. On examining the frequency of circulating CD28-ve CD4 T cells, we found significant differences between the three groups, F (2, 62) = 5.26, p = .008, η2 = .14, driven by a significant increase in the percentage of CD28-ve CD4 T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .01) and hip fracture patients without depressive symptoms (p = .04) [Figure 2b]. Similarly, differences in the frequency of circulating CD28-ve CD8 T cells were found between the three groups, F (2, 62) = 8.30, p = .001, η2 = .21, driven by a significant increase in the percentage of CD28-ve CD8 T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .001) and hip fracture patients without depressive symptoms (p = .01) [Figure 2b]. When the above analyses were repeated with adjustment for age, sex and BMI, the results remained significant (data not shown).Figure 2

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