Substantial reduction of naïve and regulatory T cells following traumatic stress

Abstract

Posttraumatic stress disorder (PTSD) is associated with an enhanced susceptibility to various somatic diseases. However, the exact mechanisms linking traumatic stress to subsequent physical health problems have remained unclear. This study investigated peripheral T lymphocyte differentiation subsets in 19 individuals with war and torture related PTSD compared to 27 non-PTSD controls (n=14 trauma-exposed controls; n=13 non-exposed controls). Peripheral T cell subpopulations were classified by their characteristic expression of the lineage markers CD45RA and CCR7 into: naïve (CD45RA(+) CCR7(+)), central memory (T(CM): CD45RA(-) CCR7(+)) and effector memory (T(EM): CD45RA(-) CCR7(-) and T(EMRA): CD45RA(-) CCR7(-)) cells. Furthermore, we analyzed regulatory T cells (CD4(+)CD25(+)FoxP3(+)) and ex vivo proliferation responses of peripheral blood mononuclear cells after stimulation with anti-CD3 monoclonal antibody. Results show that the proportion of naïve CD8(+) T lymphocytes was reduced by 32% (p=0.01), whereas the proportions of CD3(+) central (p=0.02) and effector (p=0.01) memory T lymphocytes were significantly enhanced (+22% and +34%, respectively) in PTSD patients compared to non-PTSD individuals. To a smaller extent, this effect was also observed in trauma-exposed non-PTSD individuals, indicating a cumulative effect of traumatic stress on T cell distribution. Moreover, PTSD patients displayed a 48% reduction in the proportion of regulatory T cells (p<0.001). Functionally, these alterations were accompanied by a significantly enhanced (+34%) ex vivo proliferation of anti-CD3 stimulated T cells (p=0.05). The profoundly altered composition of the peripheral T cell compartment might cause a state of compromised immune responsiveness, which may explain why PTSD patients show an increased susceptibility to infections, and inflammatory and autoimmune diseases.

Preliminary Evidence for a Compromised T-Cell Compartment in Maltreated Children with Depression and Posttraumatic Stress Disorder

“…This impact on the entire T-cell compartment is consistent with previous research in adult PTSD patients showing fewer naïve T lymphocytes but increased memory T lymphocytes [12]. Similarly, an increased ratio of memory versus naïve T cells was found in adult women with PTSD in the aftermath of childhood sexual abuse [32].…”

“…the relationship between symptom severity and increased T-cell activation [8], or to associations between PTSD and decreased counts of lymphocytes, T cells [11] and naïve T lymphocytes [12]. The number of recent thymic emigrant cells (RTEs) in the T-cell compartment [13] has been found to be persistently reduced in mice showing PTSD-like behavior due to social stress [14,15].…”

Neuroimmunoendocrine Interactions in Post-Traumatic Stress Disorder: Focus on Long-Term Implications of Childhood Maltreatment

“…Indeed, a ∼50% drop in regulatory T cells (Tregs; CD4+CD25+FoxP3+) in PTSD patients as compared to healthy controls has also been reported [1]. This substantial decline in Tregs could bear the risk of excessive inflammation due to suboptimum control of immune responses and provide further support to the pro-inflammatory profile observed in patients with PTSD.…”

“…Lymphocytes expressing the late (CD71+) but not the early (CD25+) activation marker were also elevated in displaced women. Sommershof et al [1] found an increased percentage of both central memory (CD45RA-CCR7+) and effector memory (CD45RA-CCR7-) T cell subsets in childhood abuse-related PTSD patients. Increased percentages in CD8+ T cells expressing early activation markers (CD8+CD45RA+) in abuse-related PTSD women have also been reported [38,39].…”

“…life-threatening accidents, physical assaults, sexual abuse or combat experiences), increases the risk of developing psychiatric disorders, such as post-traumatic stress disorder (PTSD). PTSD symptoms include anxiety, frequent re-experiencing of the traumatic event (in the form of intrusive recollections, nightmares or flashbacks), persistent avoidance of stimuli associated with the traumatic event and persistent symptoms of increased arousal maintaining the individual in a constant stress situation [1]. To meet the diagnostic criteria for PTSD, the traumatized subject must have had three distinct types of symptoms for at least 1 month, consisting of re-experiencing the event, avoidance of reminders of the event and hyperarousal [2].…”