Reduced numbers of naïve CD4 + T cells and an altered CD4/CD8 balance in depressed common variable immune deficiency (CVID) patients. Is thymosin-α1 a possible treatment?

Olivia Manusama, Sajni Singh, Rik A. Brooimans, Annemarie Wijkhuijs, Marianne van der Ent, Hemmo A. Drexhage*, Virgil A. Dalm

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)


In the 1990's the macrophage-T-cell-theory of depression was posed stating that low grade inflammation and an abnormal T cell system destabilize the development and function of the emotional brain in such a way, that individuals become ultrasensitive to stress. Recently we gathered evidence that indeed higher frequencies of CD4+ memory T cells, lower frequencies of naive CD4 + T cells, higher frequencies of CD8 + T cells (the latter two in part elicited by Cytomegalovirus, CMV, infection) are a characteristic of Major Depressive Disorder (MDD). In MDD patients with a history of childhood trauma and severe depression monocytes are inflammatory activated. Low grade inflammation and T cell system defects have also been reported in patients with Common Variable Immune Deficiency (CVID) (next to antibody production defects). CVID patients show a higher prevalence of mild depression. The aim of this study was to determine T cell frequencies and monocyte inflammatory activation in CVID patients with and without depression. This study confirms that CVID patients have CMV independent decreases in the frequency of naïve CD4 + T cells and it de novo shows a CMV dependent increase in the expression of inflammatory genes in monocytes. CVID patients with depression are additionally characterized by a CMV independent increase in the frequency of naïve CD8 + T cells, while lacking monocyte inflammatory activation. In conclusion, depressed CVID patients have T cell abnormalities comparable to that of patients with regular MDD. These abnormalities are presently targeted by thymosin α1 in an open-label proof of concept trial.

Original languageEnglish
Article number110168
Number of pages11
JournalInternational Immunopharmacology
Early online date20 Apr 2023
Publication statusPublished - Jun 2023

Bibliographical note

Funding Information:
This work was supported by the European Commission: EU 7th Framework program (grant number EU-FP7-CP-IP-2008–222963) and Horizon 2020 (grant number H2020-SC1-2016–2017/H2020-SC1-2017-Two-Stage-RTD) grants were received by HAD, Erasmus Medical Center Rotterdam. The funding source had no role in the study design, the data collection, the analysis and interpretation of data, the manuscript writing, and in the decision to submit the article for publication.

Publisher Copyright:
© 2023 The Author(s)


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