Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women

Abstract

Rationale The percentage of regulatory T cells (T Regs )-a subtype of T lymphocyte that suppresses the immune response-appears to be reduced in a number of stress-related diseases. The role of the T Reg in stress-disease pathways has not yet been investigated. Objectives The aim of the study was to investigate the association between biological responsivity to acute psychosocial stress and the percentage of T Regs in healthy older adults. The secondary purpose was to measure the associations between T Reg percentage and psychological and physical well-being in the participants. Methods Salivary cortisol and plasma interleukin (IL)-6 samples were obtained from 121 healthy older men and women from the Whitehall II cohort following acute psychophysiological stress testing. Three years later at a follow-up visit, we measured T Reg percentages and psychological and physical well-being were recorded using the Short Form 36 Health Survey and the Center for Epidemiologic Studies Depression Scale.Results Blunted cortisol responses (p=0.004) and elevated IL-6 responses (p=0.027) to acute psychophysiological stress were associated with greater T Reg percentage independently of age, sex, BMI, smoking status, employment grade, time of testing, and baseline measures of cortisol and IL-6, respectively. Percentage of T Regs was associated cross-sectionally with lower physical (p=0.043) and mental health status (p=0.008), and higher levels of depressive symptoms (p=0.002), independently of covariates. Conclusions Increased levels of T Regs may act as a defence against increased inflammation and may be a pre-indication for chronically stressed individuals on the cusp of clinical illness.

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

“…Our finding of increased T reg levels in MDD differs from a number of studies that have reported reduced T reg counts in depressed populations (Grosse et al, 2016b; Li et al, 2010). In contrast, our results are consistent with data from a study of elderly subjects that reported that an elevated percentage of T reg cells was associated with worse physical and mental health status, as well as higher levels of depressive symptomatology (Ronaldson et al, 2016). Our finding also is potentially consistent with several preclinical studies.…”

“…It is conceivable that an upregulation of T reg cell numbers occurs as a compensatory response to high levels of inflammation, leading to a subsequent decrease in CRP concentrations. Irrespective of the mechanism involved, the inverse association between CRP and Treg counts is consistent with a recent study reporting an inverse correlation between IL-6 responses to acute psychophysiological stress and Treg cell counts in the Whitehall II cohort (Ronaldson et al, 2016). …”

Proinflammatory T Cell Status Associated with Early Life Adversity

“…In a cohort of healthy elderly people, the percentage of Tregs was associated with lower physical and mental health and increased depression symptoms. Furthermore, in the same cohort, a greater number of Tregs was associated with a blunted cortisol response and a higher IL-6 response to an acute stressor, which was independent of confounders, such as BMI and smoking (73). Interestingly, blunted cortisol responses and increased IL-6 responses have been observed in ELA (30,74).…”

Stress-Related Immune Markers in Depression: Implications for Treatment

“…Seemingly contrary to the above-mentioned findings, recent studies investigating T-cell and monocytic inflammatory systems in bipolar and schizophrenia patients reported an elevated presence of T-reg cells in association with a monocytic inflammatory signature ( Drexhage et al, 2011a , 2011b ). Additionally, Ronaldson et al (2015) also reported an elevated T-reg cell presence in association with blunted cortisol and increased IL-6 levels in a healthy cohort of volunteers following acute stress. The elevated T-reg cell presence was also found to be correlated with worse physical and mental health status and higher levels of depressive symptomology ( Ronaldson et al, 2015 ).…”