TY - JOUR
T1 - Diagnosis-independent loss of T-cell costimulatory molecules in individuals with cytomegalovirus infection
AU - Ford, Bart N.
AU - Teague, T. Kent
AU - Bayouth, Morgan
AU - Yolken, Robert H.
AU - Bodurka, Jerzy
AU - Irwin, Michael R.
AU - Paulus, Martin P.
AU - Savitz, Jonathan
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/7
Y1 - 2020/7
N2 - 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 (CD27−CD28−) cells within CD4+ and CD8+ T-cell subsets, i.e. naive (CCR7+CD45RA+), effector memory (EM, CCR7−CD45RA−), central memory (CM, CCR7+CD45RA−) and effector memory cells re-expressing CD45RA (EMRA, CCR7−CD45RA+). 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 CD27−CD28− 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.
AB - 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 (CD27−CD28−) cells within CD4+ and CD8+ T-cell subsets, i.e. naive (CCR7+CD45RA+), effector memory (EM, CCR7−CD45RA−), central memory (CM, CCR7+CD45RA−) and effector memory cells re-expressing CD45RA (EMRA, CCR7−CD45RA+). 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 CD27−CD28− 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.
KW - Biological aging
KW - Cytomegalovirus
KW - Depression
KW - Immunosenescence
KW - Major depressive disorder
KW - Sex differences
KW - T-cells
UR - http://www.scopus.com/inward/record.url?scp=85082558832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082558832&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2020.03.013
DO - 10.1016/j.bbi.2020.03.013
M3 - Article
C2 - 32209361
AN - SCOPUS:85082558832
SN - 0889-1591
VL - 87
SP - 795
EP - 803
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -