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Selective inflammatory propensities in adopted adolescents institutionalized as infants.

ABSTRACT: This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3-21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.

SUBMITTER: Engel ML

PROVIDER: S-EPMC7880887 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The developing immune system is an adaptive system, primed by antigens, responsive to infectious pathogens, and can be affected by other aspects of the early rearing environment, including deviations from the normal provision of parental care. We investigated whether early rearing in an institutional setting, even when followed by years living in supportive and well-resourced families, would be associated with a persistent shift in T cell profiles. Immunophenotyping was used to enumerate CD4+ CD57+ and CD8+ CD57+ subsets, with gating strategies employed to differentiate naïve, central-memory, effector-memory, and terminally differentiated EM cells expressing CD45RA (TEMRA). Blood samples were collected from 96 adolescents, and PBMC isolated via Ficol gradient, followed by an optimized immunophenotypic characterization. CMV antibody titers were determined via ELISA. Adopted adolescents had lower CD4/CD8 ratios than did the control adolescents. Early rearing had a significant effect on the T cells, especially the CD8+ CD57+ CM, EM, and TEMRA cells and the CD4+ CD57+ EM cells. Adolescents who had spent their infancy in institutions before adoption were more likely to be seropositive for CMV, with higher antibody titers. CMV antibody titers were significantly correlated with the percentages of all CD8+ CD57+ cell subsets. In the statistical modeling, CMV antibody titer also completely mediated the relationship between institutional exposure and the ratio of CD4-to-CD8 cells, as well as the percentages of CD4+ CD57+ and CD8+ CD57+ subsets. These findings demonstrate that persistent immune differences are still evident even years after adoption by supportive American families. The shift in the T cells was associated with being a latent carrier of CMV and may reflect the role of specific T cell subsets in Herpes virus containment. In older adults, sustained CMV antigen persistence and immunoregulatory containment ultimately contributes to an accumulation of differentiated T cells with a decreased proliferative capacity and to immune senescence.

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Selective inflammatory propensities in adopted adolescents institutionalized as infants.

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