Abstract
Background: We have investigated the distribution of the Th1, Th2 and Th17 subsets in circulating CD4+ T lymphocytes and their naïve (TN), effector (TE), central (TCM) and effector memory (TEM) activation/differentiation stages in patients with major depressive disorder (MDD). Methods: Thirty MDD patients and 30 healthy controls were studied. The counts of circulating CD4+ T lymphocytes and their distribution on the TN, TE, TCM and TEM activation/differentiation stages were analyzed by polychromatic flow cytometry. The intracytoplasmic interferon gamma (IFNγ), interleukin (IL)-4, IL-17A and tumor necrosis factor alpha (TNF-alpha) and membrane CD28 expression were also measured. The serum IFNγ, IL-4, Il-17A and TNF-alpha were measured by Luminex, respectively. Results: MDD patients had normal counts of CD4+ T lymphocytes and of their TN, TCM and TEM subsets but increased number and percentage of TE CD4+ subset. CD4+ T lymphocytes had significantly enhanced percentage of cells that express IL-17 and TNF-alpha explained by the expansions found in the TN, TCM and, TEM and TCM, TEM and TE activation/differentiation stages, respectively. A selective increase in the percentages of TCM and TEM expressing IFNγ was also observed. We found a significant correlation between the percentages of CD4+ T lymphocytes expressing IFNγ and TNF-alpha in these patients. MDD patients showed increased serum levels of IL-17 and TNF-alpha, but normal IFNγ and IL-4 concentration. Limitations: the cross-sectional nature of the study could be considered a limitation. Conclusions: MDD patients have abnormal circulating CD4+ T lymphocytes with expansion of the IL-17 and TNF-alpha expressing cells as well as increased levels of circulating IL-17 and TNF-alpha.
Highlights
Major depressive disorder (MDD) is an exceedingly prevalent disease that causes significant disability worldwide [1]
Concerning the demographic characteristics compared between major depressive disorder (MDD) patients and healthy controls (HCs), significant differences were only found for the variable of employment status
We investigated the intracellular expression of IFNγ, IL-4, IL-17A and TNF-alpha in the total CD4+ T lymphocyte population and in the their naïve (TN), TCM, TEM and TE differentiation/activation stages among MDD patients and HCs after PMA stimulation
Summary
Major depressive disorder (MDD) is an exceedingly prevalent disease that causes significant disability worldwide [1]. Taking into account that approximately one-third of patients exhibit a poor response to MDD treatment, the need for more effective therapeutic strategies is a pressing medical objective [2]. Both experimental and human findings have underlined the relevance of abnormal immune-inflammatory response in the pathogenesis of depression [3]. CD4+ T lymphocytes are a phenotypical and regulatory diverse immune system cell population This lymphocyte heterogeneity includes different patterns of cytokine secretion and stages of differentiation/activation [5,6,7]. We have investigated the distribution of the Th1, Th2 and Th17 subsets in circulating CD4+ T lymphocytes and their naïve (TN ), effector (TE ), central (TCM ) and effector memory (TEM ) activation/differentiation stages in patients with major depressive disorder (MDD)
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