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

Background: We have investigated the distribution of the Th1, Th2 and Th17 subsets in circulating CD4(+) T lymphocytes and their naive (T-N), effector (T-E), central (T-CM) and effector memory (T-EM) 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 T-N, T-E, T-CM and T-EM activation/differentiation stages were analyzed by polychromatic flow cytometry. The intracytoplasmic interferon gamma (IFN gamma), interleukin (IL)-4, IL-17A and tumor necrosis factor alpha (TNF-alpha) and membrane CD28 expression were also measured. The serum IFN gamma, 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 T-N, T-CM and T-EM subsets but increased number and percentage of T-E 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 T-N, T-CM and, T-EM and T-CM, T-EM and T-E activation/differentiation stages, respectively. A selective increase in the percentages of T-CM and T-EM expressing IFN gamma was also observed. We found a significant correlation between the percentages of CD4(+) T lymphocytes expressing IFN gamma and TNF-alpha in these patients. MDD patients showed increased serum levels of IL-17 and TNF-alpha, but normal IFN gamma 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.