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Using flow cytometry, we determined the percentage and median fluorescence intensity of CD69, CD71, CD40L, and HLADR-bearing CD3+, CD4+, and CD8+\u2009cells, and cannabinoid type 1 receptor (CB1), CD152 and GARP (glycoprotein A repetitions predominant)-bearing CD25+\u2009FoxP3 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+\u2009FoxP3 cells or CD152 and GARP expression in combination with increases in activated T cells (especially CD8+\u2009CD40L+\u2009percentage and expression). MDD patients showed significantly increased numbers of CD3+\u2009CD71+, CD3+\u2009CD40L+, CD4+\u2009CD71+, CD4+\u2009CD40L+,  CD4+\u2009HLADR+, and CD8+\u2009HLADR+\u2009T cells, increased CD3+\u2009CD71+, CD4+\u2009CD71+\u2009and CD4+\u2009HLADR+\u2009expression, and lowered CD25+\u2009FoxP3 expression and CD25+\u2009FoxP+\u2009CB1+\u2009numbers 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+\u2009CD40L+). 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.<\/jats:p>","DOI":"10.1038\/s41598-024-61865-y","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T21:02:03Z","timestamp":1715806923000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression"],"prefix":"10.1038","volume":"14","author":[{"given":"Muanpetch","family":"Rachayon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketsupar","family":"Jirakran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimpayao","family":"Sodsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atapol","family":"Sughondhabirom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"61865_CR1","unstructured":"World Health Organisation. 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