Diagnosis-independent loss of T-cell costimulatory molecules in individuals with cytomegalovirus infection

Bart N. Ford, T. Kent Teague, Morgan Bayouth, Robert H. Yolken, Jerzy Bodurka, Michael R. Irwin, Martin P. Paulus, Jonathan Savitz

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Major depressive disorder (MDD) is associated with physiological changes commonly observed with increasing age, such as inflammation and impaired immune function. Age-related impaired adaptive immunity is characterized by the loss of naive T-cells and the reciprocal accumulation of memory T-cells together with the loss of T-cell co-stimulatory molecules. Additionally, the presence and activity of cytomegalovirus (CMV) alters the architecture of the T-cell compartment in a manner consistent with premature aging. Because CMV is also thought to reactivate with psychological stress, this study tested whether MDD influences age-related phenotypes of T-cell populations in the context of CMV infection in young and middle-aged adults. Morning blood samples from volunteers with a DSM-IV diagnosis of MDD (n = 98, mean age(SD) = 36(10) years, 74.5% female, 57.1% CMV+) and comparison controls (n = 98, mean age(SD) = 34(10) years, 68.4% female, 51.0% CMV+) were evaluated for CMV IgG antibody status and the distribution of late differentiated (CD27CD28) cells within CD4+ and CD8+ T-cell subsets, i.e. naive (CCR7+CD45RA+), effector memory (EM, CCR7CD45RA), central memory (CM, CCR7+CD45RA) and effector memory cells re-expressing CD45RA (EMRA, CCR7CD45RA+). Mixed linear regression models controlling for age, sex, ethnicity and flow cytometry batch showed that CMV seropositivity was associated with a reduction in naive T-cells, expansion of EMRA T-cells, and a greater percent distribution of CD27CD28 cells within CD4+ and CD8+ memory T-cell subsets (p's < 0.004), but there was no significant effect of MDD, nor any significant interaction between CMV and diagnosis. Unexpectedly, depressed men were less likely to be CMV+ and depressed women were more likely to be CMV+ than sex-matched controls suggesting a possible interaction between sex and MDD on CMV susceptibility, but this three-way interaction did not significantly affect the T-cell subtypes. Our findings suggest that depression in young and middle-aged adults does not prematurely advance aging of the T-cell compartment independently of CMV, but there may be significant sex-specific effects on adaptive immunity that warrant further investigation.

Original languageEnglish
Pages (from-to)795-803
Number of pages9
JournalBrain, Behavior, and Immunity
Volume87
DOIs
StatePublished - Jul 2020
Externally publishedYes

Keywords

  • Biological aging
  • Cytomegalovirus
  • Depression
  • Immunosenescence
  • Major depressive disorder
  • Sex differences
  • T-cells

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