Major depression favors the expansion of Th17-like cells and decrease the proportion of CD39+Treg cell subsets in response to myelin antigen in multiple sclerosis patients.

BACKGROUND: Mood disorders have been associated with risk of clinical relapses in multiple sclerosis (MS), a demyelinating disease mediated by myelin-specific T cells. OBJECTIVES: We aimed to investigate the impact of major depressive disorder (MDD) and cytokine profile of T-cells in relapsing remitting MS patients. METHODS: For our study, plasma and PBMC were obtained from 60 MS patients (30 with lifetime MDD) in remission phase. The PBMC cultures were stimulated with anti-CD3/anti-CD28 beads or myelin basic protein (MBP), and effector and regulatory T cell phenotypes were determined by flow cytometry. The cytokine levels, both in the plasma or in the supernatants collected from PBMC cultures, were quantified by Luminex. In some experiments, the effect of serotonin (5-HT) was investigated. RESULTS: Here, higher Th17-related cytokine levels in response to anti-CD3/anti-CD28 and MBP were quantified in the plasma and PBMC cultures of the MS/MDD group in comparison with MS patients. Further, elevated frequency of CD4+ and CD8+ T cells capable of producing IL-17, IL-22 and GM-CSF was observed in depressed patients. Interestingly, the percentage of myelin-specific IFN-γ+IL-17+ and IFN-γ+GM-CSF+ CD4+ T cells directly correlated with neurological disabilities. In contrast, the occurrence of MDD reduced the proportion of MBP-specific CD39+Tregs subsets. Notably, the severity of both neurological disorder and depressive symptoms inversely correlated with these Tregs. Finally, the addition of 5-HT downregulated the release of Th17-related cytokines in response to anti-CD3/anti-CD28 and myelin antigen. CONCLUSIONS: In summary, our findings suggested that recurrent major depression, by favoring imbalances of effector Th17 and Treg cell subsets, contributes to MS severity.

Phenotypic and Functional Analysis of T Follicular Cells in Common Variable Immunodeficiency.

INTRODUCTION: One of the most frequent abnormalities of B cells in common variable immunodeficiency (CVID) is reduced number of class-switched memory B cells, suggesting an impaired germinal center response. Therefore, due to its pivotal role in regulating the development of humoral immunity, the objective of this study was to evaluate the role of circulating T follicular helper (cTFH) and circulating T follicular regulatory (cTFR) cells in the pathogenesis of CVID. METHODS: cTFH and cTFR cells from CVID patients and healthy subjects were phenotypically characterized by flow cytometry. cTFH and memory B cells from CVID patients and healthy subjects were isolated and cocultured. RESULTS: Our results showed a reduced proportion of cTFH17 cells in patients with CVID and an increased ratio of cTFH/cTFR cells in CVID patients with autoimmune diseases. Furthermore, the proportion of IL-21-producing cTFH cells was directly related to the proportion of CD27+ IgD- B cells. Interestingly, coculture assay showed that CVID-derived cTFH cells are able to help memory B cells from healthy controls to produce immunoglobulins. CONCLUSIONS: The proportions of cTFH17 and cTFR cells are altered in CVID patients; however, the cTFH function in assisting B cells to produce antibodies in vitro is preserved.