Expansion of CD4 T Lymphocytes Expressing Interleukin 17 and Tumor Necrosis Factor in Patients with Major Depressive Disorder

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.