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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 T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) The percentage of CD3+ve T cells in healthy controls: n = 37; hip fracture patients without depression (HF): n = 38 and hip fracture patients with depressive symptoms (HF + D): n = 29.The solid bar represents the mean value. (b) The mean absolute number of T cells in healthy controls: n = 20; hip fracture patients without depression (HF): n = 19 and hip fracture patients with depressive symptoms (HF + D): n = 15. Data are mean ± SEM. *p < .05 and **p < .01. Representative flow cytometry plots and gating strategy of PBMCs from a young individual stained with anti-CD3 and (c) anti-CD4, and CD8, (d) and anti-CD45RA and -CCR7 (e and f).
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Fig1: Frequency of peripheral T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) The percentage of CD3+ve T cells in healthy controls: n = 37; hip fracture patients without depression (HF): n = 38 and hip fracture patients with depressive symptoms (HF + D): n = 29.The solid bar represents the mean value. (b) The mean absolute number of T cells in healthy controls: n = 20; hip fracture patients without depression (HF): n = 19 and hip fracture patients with depressive symptoms (HF + D): n = 15. Data are mean ± SEM. *p < .05 and **p < .01. Representative flow cytometry plots and gating strategy of PBMCs from a young individual stained with anti-CD3 and (c) anti-CD4, and CD8, (d) and anti-CD45RA and -CCR7 (e and f).

Mentions: Peripheral T cells counts in hip fracture patients with and without depressive symptoms were compared with healthy older adults. Significant differences in percentages of CD3+ve T cells in the PBMC pool were found between the three groups, F (2, 101) = 4.59, p = .01, η2 = .08, [Figure 1a], which was driven by a significant decline in percentage of T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .01) but not with hip fracture patients without depressive symptoms (p = .12). Similarly, on examining the absolute numbers of T cells in peripheral blood, significant differences were seen between our three groups, F (2, 51) = 7.18, p = .002, η2 = .22 [Figure 1b], with a decline shown in T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .003). When the above analyses were repeated with adjustment for age, sex and BMI, the results remained significant (data not shown).Figure 1


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 T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) The percentage of CD3+ve T cells in healthy controls: n = 37; hip fracture patients without depression (HF): n = 38 and hip fracture patients with depressive symptoms (HF + D): n = 29.The solid bar represents the mean value. (b) The mean absolute number of T cells in healthy controls: n = 20; hip fracture patients without depression (HF): n = 19 and hip fracture patients with depressive symptoms (HF + D): n = 15. Data are mean ± SEM. *p < .05 and **p < .01. Representative flow cytometry plots and gating strategy of PBMCs from a young individual stained with anti-CD3 and (c) anti-CD4, and CD8, (d) and anti-CD45RA and -CCR7 (e and f).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Frequency of peripheral T lymphocytes in hip fracture patients with and without depressive symptoms versus healthy controls. (a) The percentage of CD3+ve T cells in healthy controls: n = 37; hip fracture patients without depression (HF): n = 38 and hip fracture patients with depressive symptoms (HF + D): n = 29.The solid bar represents the mean value. (b) The mean absolute number of T cells in healthy controls: n = 20; hip fracture patients without depression (HF): n = 19 and hip fracture patients with depressive symptoms (HF + D): n = 15. Data are mean ± SEM. *p < .05 and **p < .01. Representative flow cytometry plots and gating strategy of PBMCs from a young individual stained with anti-CD3 and (c) anti-CD4, and CD8, (d) and anti-CD45RA and -CCR7 (e and f).
Mentions: Peripheral T cells counts in hip fracture patients with and without depressive symptoms were compared with healthy older adults. Significant differences in percentages of CD3+ve T cells in the PBMC pool were found between the three groups, F (2, 101) = 4.59, p = .01, η2 = .08, [Figure 1a], which was driven by a significant decline in percentage of T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .01) but not with hip fracture patients without depressive symptoms (p = .12). Similarly, on examining the absolute numbers of T cells in peripheral blood, significant differences were seen between our three groups, F (2, 51) = 7.18, p = .002, η2 = .22 [Figure 1b], with a decline shown in T cells in hip fracture patients with depressive symptoms compared with healthy controls (p = .003). When the above analyses were repeated with adjustment for age, sex and BMI, the results remained significant (data not shown).Figure 1

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