Substantial reduction of naïve and regulatory T cells following traumatic stress.
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.
Sommershof
Annette
A
Division of Immunology, University of Konstanz, Konstanz, Germany.
Aichinger
Hannah
H
Engler
Harald
H
Adenauer
Hannah
H
Catani
Claudia
C
Boneberg
Eva-Maria
EM
Elbert
Thomas
T
Groettrup
Marcus
M
Kolassa
Iris-Tatjana
IT
D000328:Adult; D000704:Analysis of Variance; D002452:Cell Count; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D003130:Combat Disorders / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011581:Psychological Tests; D013313:Stress Disorders, Post-Traumatic / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*