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

Hideo Suzuki, Jonathan Savitz, T. Kent Teague, Siva K. Gandhapudi, Chibing Tan, Masaya Misaki, Brett A. McKinney, Michael R. Irwin, Wayne C. Drevets, Jerzy Bodurka

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations. Furthermore, despite evidence that sleep disturbance, which is a core symptom of MDD, is itself associated with alterations in lymphocyte distributions, there is a paucity of studies examining the contribution of sleep disturbance on lymphocyte populations in MDD populations. Here, we measured differences in the percentages of 13 different lymphocytes and 6 different leukocytes in 54 unmedicated MDD patients (partially remitted to moderate) and 56 age and sex-matched healthy controls (HC). The relationship between self-reported sleep disturbance and cell counts was evaluated in the MDD group using the Pittsburgh Sleep Quality Index (PSQI). The MDD group showed a significantly increased percentage of CD127low/CCR4+ Treg cells, and memory Treg cells, as well as a reduction in CD56+CD16 (putative immunoregulatory) NKC counts, the latter, prior to correction for body mass index. There also was a trend for higher effector memory CD8+ cell counts in the MDD group versus the HC group. Further, within the MDD group, self-reported sleep disturbance was associated with an increased percentage of effector memory CD8+ cells but with a lower percentage of CD56+CD16 NKC. These results provide important new insights into the immune pathways involved in MDD, and provide novel evidence that MDD and associated sleep disturbance increase effector memory CD8+ and Treg pathways. Targeting sleep disturbance may have implications as a therapeutic strategy to normalize NKC and memory CD8+ cells in MDD.

Original languageEnglish (US)
Pages (from-to)193-200
Number of pages8
JournalBrain, Behavior, and Immunity
StatePublished - Nov 2017


  • CD8 cells
  • Depression
  • Flow cytometry
  • Natural killer cells
  • Regulatory T cells
  • Sleep

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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