Proinflammatory T Cell Status Associated with Early Life Adversity

Abstract

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( = 42) and those without a history of ELA (control, = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69CD8 T cells ( = 0.022), increased numbers of HLA-DR CD4 and HLA-DR CD8 T cells ( < 0.001), as well as increased numbers of CD25CD8 T cells ( = 0.036). ELA also showed a trend toward higher numbers of CCR4CXCR3CCR6 CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells.

From early adversities to immune activation in psychiatric disorders: the role of the sympathetic nervous system

“…Comparing individuals separated from their mothers in early life to those reared by their parents, Elwenspoek and colleagues also reported increased T cell senescence (CD57 + cells) . In another FACS study from this group, comparing individuals with a history of ELA to those without, a reduction in the numbers of CD69 + /CD8 + T cells and increased numbers of human leucocyte antigen D‐related HLA‐DR + /CD4 + , HLA‐DR + /CD8 + and CD25 + /CD8 + T cells was reported . Collectively, these results suggest that ELA exposure is associated with a sustained activation of adaptive immunity and accelerated immune ageing, as indexed by the increase in T cell senescence.…”

“…Collectively, these results suggest that ELA exposure is associated with a sustained activation of adaptive immunity and accelerated immune ageing, as indexed by the increase in T cell senescence. These effects appeared to be independent of either stress or health‐risk behaviours, suggestive of a primary effect of early life programming on specific immune cell populations . Exploring how social adversity may affect peripheral immune cells, Counotte et al .…”

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“…ELA clearly accelerated T-lymphocyte maturation and senescence, although did not affect B cells. T-lymphocytes were accelerated through their maturation cycle from naïve to effector memory and aggregating in the terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) cell phase [27,28]. This skewing of the immune system, in particular the cytotoxic CD8+ T-cells was confirmed in an independent cohort, of teenagers approximately 15 years after a similar form of ELA [29].…”

“…We have outlined above the ELA-induced long term immunophenotype. Although the origins are multifactorial, it would appear, from the work of Elwenspoek [27,28] and Reid [29], that an adverse social environment in early life drive T-cells, in particular CD8+ CTLs, towards a senescent state. When the different aspects of ELA are considered separately, immunosenescence would appear to be a common aspect.…”

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“…This mode of protection is typically lost when maternally derived antibodies are degraded, but the maturing offspring immune system's ability to generate its own effective adaptive immunity replaces it [56]. A wide body of research highlights the fundamental role early-life environment plays in determining the broad transcriptional identity of circulating lymphocytes and showing that the early-life environment has a very strong influence on T-cells [57][58][59][60][61][62].…”