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 naïve (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 (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 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 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.