A population of atypical CD56(-)CD16(+) natural killer cells is expanded in PTSD and is associated with symptom severity

Research output: Contribution to journalArticle


INTRODUCTION: Post-traumatic stress disorder (PTSD) has been associated with immune disturbances, including a higher incidence of infections and autoimmune diseases as well as a net pro-inflammatory state. Natural killer (NK) cells, a key component of the innate immune system, have been less well-studied in PTSD despite their importance in immunity.

METHODS: We studied two independent samples of combat-exposed male war veterans with or without PTSD, the first ("Discovery Sample") to generate hypotheses, and the second ("Validation Sample") to replicate the findings. The Discovery Sample was comprised of 42 PTSD subjects and 42 controls. The Validation Sample was comprised of 25 PTSD subjects and 30 controls. Participants had fasting, morning blood samples collected for examination of the frequency of NK cell subsets, determined by flow cytometry. The current and lifetime Clinician Administered PTSD Scale (CAPS) was used to assess symptom severity. Statistical analyses were adjusted for age and BMI.

RESULTS: PTSD subjects compared to controls had (i) a significantly higher relative frequency of atypical CD56(-)CD16(+) NK cells in the Discovery Sample (p=0.027), which was replicated in the Validation Sample (p=0.004) and the combined sample (p<0.001), and (ii) a non-significantly lower relative frequency of CD56(bright)CD16(-) NK cells in the two samples (p=0.082; p=0.118), which became statistically significant in the combined sample (p=0.020). Further, within subjects with PTSD of both samples, the relative frequency of atypical CD56(-)CD16(+) NK cells was near significantly positively correlated with lifetime PTSD severity (p=0.074).

DISCUSSION: This study is the first to characterize NK cell subsets in individuals with PTSD. The results suggest that combat-exposed men with PTSD exhibit an aberrant profile of NK cells with significantly higher frequencies of an atypical population of CD56(-)CD16(+) cells and possibly lower frequencies of the functional CD56(bright)CD16(-) NK cell subsets. Higher proportions of dysfunctional CD56(-)CD16(+) cells have been reported in certain chronic viral infections and in senescent individuals. It is possible that this could contribute to immune dysfunctions and prematurely senescent phenotypes seen in PTSD.


  • Francesco S Bersani
  • Owen M Wolkowitz
  • Jeffrey M Milush
  • Elizabeth Sinclair
  • Lorrie Eppling
  • Kirstin Aschbacher
  • Daniel Lindqvist
  • Rachel Yehuda
  • Janine Flory
  • Linda M Bierer
  • Iouri Matokine
  • Duna Abu-Amara
  • Victor I Reus
  • Michelle Coy
  • Christina M Hough
  • Charles R Marmar
  • Synthia H Mellon
External organisations
  • University of California System
  • Icahn School of Medicine at Mount Sinai
  • New York University
  • University of California, San Francisco
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)264-270
Number of pages7
JournalBrain Behavior and Immunity
Issue numberAugust 2016
Early online date2016 Mar 26
Publication statusPublished - 2016 Aug
Publication categoryResearch