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. 2024 May 16;14(1):11177.
doi: 10.1038/s41598-024-61865-y.

T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression

Muanpetch Rachayon  1 , Ketsupar Jirakran  1   2 , Pimpayao Sodsai  3 , Atapol Sughondhabirom  1 , Michael Maes  4   5   6   7   8   9
Affiliations

T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression

Muanpetch Rachayon et al. Sci Rep. .

Abstract

Major depressive disorder (MDD) is associated with T cell activation, but no studies have examined the combined effects of T cell activation and deficits in T regulatory (Treg) cells on the severity of acute phase MDD. Using flow cytometry, we determined the percentage and median fluorescence intensity of CD69, CD71, CD40L, and HLADR-bearing CD3+, CD4+, and CD8+ cells, and cannabinoid type 1 receptor (CB1), CD152 and GARP (glycoprotein A repetitions predominant)-bearing CD25+ FoxP3 T regulatory (Treg) cells in 30 MDD patients and 20 healthy controls in unstimulated and stimulated (anti-CD3/CD28) conditions. Based on cytokine levels, we assessed M1 macrophage, T helper (Th)-1 cell, immune-inflammatory response system (IRS), T cell growth, and neurotoxicity immune profiles. We found that the immune profiles (including IRS and neurotoxicity) were significantly predicted by decreased numbers of CD152 or GARP-bearing CD25+ FoxP3 cells or CD152 and GARP expression in combination with increases in activated T cells (especially CD8+ CD40L+ percentage and expression). MDD patients showed significantly increased numbers of CD3+ CD71+, CD3+ CD40L+, CD4+ CD71+, CD4+ CD40L+, CD4+ HLADR+, and CD8+ HLADR+ T cells, increased CD3+ CD71+, CD4+ CD71+ and CD4+ HLADR+ expression, and lowered CD25+ FoxP3 expression and CD25+ FoxP+ CB1+ numbers as compared with controls. The Hamilton Depression Rating Scale score was strongly predicted (between 30 and 40% of its variance) by a lower number of CB1 or GARP-bearing Treg cells and one or more activated T cell subtypes (especially CD8+ CD40L+). In conclusion, increased T helper and cytotoxic cell activation along with decreased Treg homeostatic defenses are important parts of MDD that lead to enhanced immune responses and, as a result, neuroimmunotoxicity.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Partial regression of the total Hamilton Depression Rating Scale (HAMD) score on baseline number of CD4+ CD40L+ cells.
Figure 2
Figure 2
Partial regression of the total Hamilton Depression Rating Scale (HAMD) score on baseline number of CD4+ CD71+ cells.
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