Preprint Article Version 1 This version is not peer-reviewed

Impairments in Peripheral Blood T Effector and T Regulatory Lymphocytes in Bipolar Disorder are Associated with Staging of Illness and Anti-cytomegalovirus IgG Levels

Version 1 : Received: 10 March 2020 / Approved: 11 March 2020 / Online: 11 March 2020 (10:45:16 CET)

How to cite: Maes, M.; Nani, J.; Noto, C.; Rizzo, L.; Hayashi, M.; Brietzke, E. Impairments in Peripheral Blood T Effector and T Regulatory Lymphocytes in Bipolar Disorder are Associated with Staging of Illness and Anti-cytomegalovirus IgG Levels. Preprints 2020, 2020030186 (doi: 10.20944/preprints202003.0186.v1). Maes, M.; Nani, J.; Noto, C.; Rizzo, L.; Hayashi, M.; Brietzke, E. Impairments in Peripheral Blood T Effector and T Regulatory Lymphocytes in Bipolar Disorder are Associated with Staging of Illness and Anti-cytomegalovirus IgG Levels. Preprints 2020, 2020030186 (doi: 10.20944/preprints202003.0186.v1).

Abstract

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined T cell subsets both before and after ex vivo anti CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 euthymic BD patients and 21 healthy controls as well as human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of baseline (unstimulated) CD3+CD8+CD71+ and CD4+CD25+FOXP3 and increased CD4+CD25+FOXP3+CD152+ frequencies and with lowered stimulated frequencies of CD3+CD8+CD71+, CD4+CD25+FOXP3+CD152+ and CD4+CD25+FOXP3+GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3+CD4+CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4+CD25+FOXP+GARP T phenotypes. In conclusion, BD is characterized by deficits in immune-regulatory functions while the staging of illness is characterized by additional impairments is Teff and Treg activation. HCMV seropositivity may contribute to an immune-risk phenotype associated with BD.

Subject Areas

bipolar depression; inflammation; neuroimmunomodulation; cytokines; psychoneuroimmunology; staging

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