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Introduction: Obesity can complicate IgE-mediated allergic diseases. In the present study, we aimed to investigate the ability of obesity-related concentrations of leptin to modulate the in vitro effector and regulatory Fel d1-specific CD4 + T-cell subsets in patients allergic to cat, considered the third most common cause of respiratory allergy in humans., Methods: For this study, plasma and peripheral blood mononuclear cells (PBMC) from 30 cat-allergic patients with mild, moderate and severe respiratory symptoms were obtained. The PBMC cultures were stimulated with Fel d1 antigen (10 µg/mL) in the presence or absence of obesity-related leptin dose (50 ηg/mL). After 6 days, the levels of cytokines and IgE in the supernatants were evaluated by multiplex and ELISA, respectively. The frequency of different non-follicular (CXCR5 - ) and follicular (CXCR5 + ) Fel d1-specific CD4 + T cell subsets was determined by flow cytometry. The plasma levels of leptin and IgE anti-cat titers were evaluated by ELISA and ImmunoCAP, respectively., Results and Conclusions: Fel d1 induced both IgE production and release of cytokines related to Th2, Th9 and Th17 cell phenotypes. Feld1 was more efficient in increasing the frequency of T FH IL-21 - cells positive for IL-4, IL-5 and IL-13 than T FH IL-21 + cell subsets. Leptin favored the expansion Th2-like and Th9-like cells and T FH IL-21 - cells positive for IL-4, IL-5 and IL-13, but reduced the proportion of conventional (Treg/Tr-1) and follicular (T FR ) regulatory CD4 + T-cell subsets expressing or not CD39 marker. Finally, many of the imbalances between Fel d1-specific CD4 + T-cells were also correlated with plasma leptin and anti-Fel d1 IgE titers. In summary, hyperleptinemia should negatively impact on the severity of cat allergies by favoring the expansion of pathogenic Fel d1-specific CD4 + T-cell phenotypes and damaging the functional status of regulatory CD4 + T-cell subsets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vollmer, Dias, Sales, Sacramento, Silva, Oyamada, Linhares, Gupta, Kasahara and Bento.)

Background: Obesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4 + T-cell subsets from lean, overweight and obese AA patients., Methods: Mononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4 + T-cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese-related leptin dose on cytokine production and Treg cell function in AA-derived CD4 + T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese., Results: AA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17-like cells rather than classic Th2-like cells. On the other hand, the frequencies of Th1-like, Br1 cells and regulatory CD4 + T-cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17-like cells positively correlated with leptin levels, the frequencies of regulatory CD4 + T-cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity-related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4 + T cell cultures from lean AA patients., Conclusion: In summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17-like and Th2/Th17 cells and decreasing regulatory CD4 + T cell subsets, being adverse effects probably mediated by leptin overproduction., Competing Interests: All authors declare that there are no conflicts of interest., (© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Recent evidences have suggested the involvement of toll-like receptor (TLR)-4 in the pathogenesis of cerebral cavernous malformations (CCM). Elevated frequency of TLR + T-cells has been associated with neurological inflammatory disorders. As T-cells and B-cells are found in CCM lesions, the objective of the present study was to evaluate the cytokine profile of T-cells expressing TLR2 and TLR4, as well as B-cell subsets, in asymptomatic (CCM Asympt ) and symptomatic (CCM Sympt ) patients., Methods: For our study, the cytokine profile from TLR2 +  and TLR4 +  T-cell and B-cell subsets in CCM Asympt and CCM Sympt  patients was investigated using flow cytometry and ELISA. T-cells were stimulated in vitro with anti-CD3/anti-CD28 beads or TLR2 (Pam3C) and TLR4 (LPS) ligands., Results: CCM Symptc  patients presented a higher frequency of TLR4 + (CD4 + and CD8 + ) T-cells and greater density of TLR4 expression on these cells. With regard to the cytokine profile, the percentage of TLR2 + and TLR4 + Th17 cells was higher in CCM Sympt patients. In addition, an elevated proportion of TLR4 +  Tc-1 cells, as well as Tc-17 and Th17.1 cells expressing TLR2 and TLR4, was observed in the symptomatic patients. By contrast, the percentage of TLR4 + IL-10 + CD4 +  T cells was higher in the CCM Asympt  group. Both Pam3C and LPS were more able to elevate the frequency of IL-6 + CD4 + T cells and Th17.1 cells in CCM Sympt  cell cultures. Furthermore, in comparison with asymptomatic patients, purified T-cells from the CCM Sympt group released higher levels of Th17-related cytokines in response to Pam3C and, mainly, LPS, as well as after activation via TCR/CD28. Concerning the B-cell subsets, a higher frequency of memory and memory activated B-cells was observed in CCM Sympt patients., Conclusions: Our findings reveal an increase in circulating Th17/Tc-17 cell subsets expressing functional TLR2 and, mainly, TLR4 molecules, associated with an increase in memory B-cell subsets in CCM patients with clinical activity of the disease., (© 2022. The Author(s).)

Elevated frequency of Th17-like cells expressing Toll-like receptors (TLRs) has been recently associated with relapsing-remitting multiple sclerosis (MS) pathogenesis, a chronic inflammatory demyelinating autoimmune disease of the central nervous system. We aimed to investigate the impact of current major depressive disorder (MDD) on the behaviour of these cells following in vitro stimulation with TLR2, TLR4, TLR5 and TLR9 agonists. Here, the level of both cell proliferation and cytokine production related to Th17/Tc17 phenotypes in response to TLR2 (Pam3C) and TLR4 (LPS) ligands was significantly higher in CD4 + and CD8 + T-cell cultures from MS/MDD patients when compared to non-depressed patients. These cytokine levels were positively associated with neurological disabilities in patients. No difference for responsiveness to TLR5 (flagellin) and TLR9 (ODN) agonists was observed. LPS, but not Pam3C, induced significant IL-10 release, mainly in patients without MDD. Interestingly, more intense expression of TLR2 and TLR4 on these cells was observed in MDD patients. Finally, in vitro addition of serotonin and treatment of MDD patients with selective serotonin reuptake inhibitors (SSRIs) reduced the production of Th17/Tc17-related cytokines by CD4 + and CD8 + T cells in response to Pam3C and LPS. However, only SSRI therapy diminished the frequency and intensity of TLR2 and TLR4 expression on circulating CD4 + and CD8 + T cells. In summary, although preliminary, our findings suggest that adverse events that elevate circulating levels of TLR2 and TLR4 ligands can affect MS pathogenesis, particularly among depressed patients., (© 2020 John Wiley & Sons Ltd.)

Circulating T FH (cT FH ) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cT FH 1, cT FH 2, cT FH 17, and cT FR cells, respectively. This CD4 + T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cT FH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-β-estradiol (E2) directly increased the percentage of different cT FH subsets. While E2 and progesterone (P4) increased the proportion of differentiated T FH cells derived from naïve CD4 + T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/T FH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10 + T FR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT FH and B cell subsets., (© 2020 Wiley-VCH GmbH.)

Introduction: Major depressive disorder (MDD) can impact the severity of allergic rhinitis (AR) and asthma (AA). Here, we evaluated the cytokine production by T-cells from AR and AA patients with or without MDD. The effect of serotonin on the in vitro T-cell response was also evaluated., Methods: The cytokines produced by activated T-cells were measured by Luminex and flow cytometry. In some cell cultures, serotonin was added., Results: MDD not only enhanced the production of Th2- and Th17-related cytokines, but also, the levels of interleukin (IL)-5 and IL-17 were directly correlated with the severity of depression and anxiety symptoms. As compared with AR, the levels of IL-17 were higher and the release of IL-10 was lower in activated T-cell cultures from AA patients, mainly those with MDD. In AA/MDD patients, the severity of anxiety symptoms and lung disease was directly correlated with Th17-like and hybrid Th2/Th17 cells, but inversely correlated with IL-10-secreting CD4+ T-cells. Finally, the addition of serotonin reduced the production of Th2- and Th17-related cytokines, but elevated IL-10 secretion in cell cultures from both AR and AA patients., Conclusions: Our findings suggest that not only the occurrence of MDD but also the severity of anxiety symptoms, may adversely affect the outcome of allergic reactions by favoring the production of cytokines implicated in the pathogenesis of AR and AA, a phenomenon that was attenuated by serotonin., (© 2021 S. Karger AG, Basel.)

Selective IgM deficiency (SIgMD) is a rare immunodeficiency characterized by serum IgM below two standard of mean, and normal IgG and IgA levels. Both in human and mice with selective IgM deficiency, germinal centers cells are decreased. The development of germinal center and humoral immunity are regulated in part by follicular helper T (T FH ) and follicular regulatory T (T FR ) cells. However, the analysis of circulating T FH (cT FH ) and T FR (cT FR ) cells in the pathogenesis of SIgMD has not been explored. We observed lower percentage of cT FR cells in SIgMD patients than in control group. However, we did not observe any significant difference in the percentage of cT FH cells and their subsets between both experimental groups. When data were analyzed according to specific antibody response to pneumococcal polysaccharide, we observed a higher percentage of cT FH cells in SIgMD patients with specific antibody deficiency than in SIgMD patients with normal specific antibody response. Our results suggest that cT FH cells and their subsets are preserved in SIgMD patients. However, the role of lower percentage of cT FR cells in the pathogenesis of this immunodeficiency is not clear., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Problem: Pregnancy appears to favor maternal antibody production. In contrast, by damaging follicular helper T cells (T FH ), HIV-1 infection compromises protective humoural immune response. Therefore, we aimed to investigate the frequency of different T FH -like cells in HIV-infected pregnant women (PW) before and after antiretroviral (ARV) therapy., Method of Study: Peripheral blood mononuclear cells, CD4 + T and B cells, were obtained from asymptomatic HIV-1-infected non-PW and PW just before and after ARV therapy. In some experiments, healthy HIV-1-negative PW were also tested. The frequency of different T FH -like cell subsets was determined by flow cytometry. The plasma titers of IgG anti-tetanus toxoid (TT), anti-HBsAg, and anti-gp41 were determined by ELISA. The in vitro production of total IgG, IL-21, and hormones (estrogen and progesterone) was quantified also by ELISA., Results: Our results demonstrate that antiretroviral (ARV) therapy was more efficient in elevating the percentage of circulating IL-21-secreting T FH cells in HIV-1-infected pregnant women (PW) than in non-pregnant patients (nPW). Moreover, in co-culture systems, CD4 + T cells from ART-treated PW were more efficient in assisting B cells to produce IgG production. The in vivo anti-HBsAg IgG titers after ARV therapy were also significantly higher in PW, and their levels were directly associated with both IL-21 + T FH frequency and plasma concentration of estrogen., Conclusion: In summary, our results suggest that pregnancy favors the recovery of T FH -like cells after ARV therapy in HIV-1-infected women, which could help these mothers to protect their newborns from infectious diseases by transferring IgG across the placenta., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2020 S. Karger AG, Basel.)

Chronic hepatitis C (CHC) is frequently related to liver fibrosis, and several studies have suggested that the immunological activity of HCV antigens contributes to hepatic damage. In the present study, among structural and non-structural HCV antigens, elevatedIL-1β, IL-6, IL-17 levels were secreted by PBMC cultures obtained from CHC patients following stimulation with core antigen. Moreover, the percentage of core-specific IL-6 + IL-17 + (CD4 + and CD8 + ) T cells was significantly higher in patients with worsehepatic lesions, determined on the Metavir scale. When compared with healthy subjects, the percentage of circulating Treg cells was elevated in CHC patients, mainly among those with advanced liver fibrosis. Nevertheless, in this last group of patients, the proportion of CD39 + Treg subsets was very low. Finally, the percentage of senescent (CD57 + CD28 - ) and exhausted (PD-1 + CD28 + ) core-specific T cells in CHC patients was also found to be a result of fibrotic hepatic status. In summary, imbalances between different core-specific T cell subsets are associated with liver fibrosis severity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: High frequency of circulating Th17 cell subsets expressing TLR2, TLR4 and TLR9 was observed in Neuromyelitis optica spectrum disorder (NMOSD) patients, a severe humoral autoimmune disease of the central nervous system. Our objective was to evaluate the direct effects of different TLR ligands on CD4 + T-cells form those patients., Methods: CD4 + T-cell cultures from NMOSD and healthy individuals were stimulated with different TLR ligands and the cell proliferation and cytokine profile was analyzed by [ 3 H] TdR up take and ELISA/ cytometry, respectively. The plasma levels of CD14 were determined by ELISA., Results: Here, Pam3C (TLR2) and LPS (TLR4) induced significant cell proliferation and IL-6, IL-17 and IL-21 production by CD4 + T-cells from NMOSD. Additionally, while both TLR ligands were more potent in favoring the expansion of T FH -like cells, Pam3C reduced the frequency of IL-10-secreting FoxP3 + and FoxP3 - CD4 + T-cells. With regard to disease severity, the levels of IL-6, IL-17 and IL-21 produced by CD4 + T-cells, as well as the frequency of T FH -like cells, in response to TLR2 and TLR4 agonists were positively correlated with neurological disabilities and the occurrence of new acute relapses during follow up. Finally, circulating levels of CD14, an indirect marker of microbial translocation, were positively correlated with IL-6, IL-17 and IL-21 release by Pam3C- and LPS-activated CD4 + T-cells., Conclusions: In summary, our data suggest that microbial antigens may affect NMOSD outcomes by favoring an imbalance between Th17 and TFH-like cells and regulatory T cell subsets., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Both obesity and low vitamin D levels have been associated with allergic asthma (AA) severity. In the present study, severity of AA was associated with obesity but to the in vitro IgE production. In those patients, higher levels of IL-5, IL-6 and IL-17 were quantified in CD4 + T-cell cultures as compared with patients with mild and moderate AA. In addition, the lowest IL-10 levels were detected in the cell cultures from patients with a worse prognosis. Interestingly, the occurrence of AA elevates the plasma levels of leptin, and this adipokine was positively correlated with the release of IL-5, IL-6 and IL-17, but inversely correlated with IL-10 production, by CD4 + T-cells from patients. In AA-derived CD4 + T-cell cultures, 1,25(OH)2D3 was less efficient at inhibiting IL-5, IL-6 and IL-17 production, and up regulating IL-10 release, as those from healthy subjects. Interestingly, the in vitro immunomodulatory effects of vitamin D were inversely correlated with serum leptin levels. In summary, our findings suggested that obesity, probably due to the overproduction of leptin, negatively impacts AA as it favors imbalance between Th2/Th17 and regulatory phenotypes. The deleterious effects of leptin may also be due to its ability to counter-regulate the immunosuppressive effects of vitamin D., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Due to their function in assisting B cells, T FH cells may be involved in the production of pathogenic IgG in neuromyelitis optica spectrum disorder (NMOSD). In the present study, the proportion of IL-6 + and IL-17 + T FH cell subsets was higher in NMOSD patients than healthy individuals. The frequency of both T FH cell subsets were directly associated with disease activity. By contrast, NMOSD patients with a higher proportion of IL-10 + T FH cell subsets showed a lower neurological disabilities score. In summary, all findings suggest that expansion of peripheral IL-6 + and IL-17 + T FH cells may be involved in the severity of NMOSD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Euphorbia umbellata (E. umbellata) belongs to Euphorbiaceae family, popularly known as Janauba, and its latex contains a combination of phorbol esters with biological activities described to different cellular protein kinase C (PKC) isoforms. Here, we identified deoxi-phorbol esters present in E. umbellata latex alcoholic extract that are able to increase HIV transcription and reactivate virus from latency models. This activity is probably mediated by NF-kB activation followed by nuclear translocation and binding to the HIV LTR promoter. In addition, E. umbellata latex extract induced the production of pro inflammatory cytokines in vitro in human PBMC cultures. This latex extract also activates latent virus in human PBMCs isolated from HIV positive patients as well as latent SIV in non-human primate primary CD4+ T lymphocytes. Together, these results indicate that the phorbol esters present in E. umbellata latex are promising candidate compounds for future clinical trials for shock and kill therapies to promote HIV cure and eradication., Competing Interests: The authors have declared that no competing interests exist.

Excessive levels of proinflammatory cytokines in the CNS are associated with reduced serotonin (5-HT) synthesis, a neurotransmitter with diverse immune effects. In this study, we evaluated the ability of exogenous 5-HT to modulate the T-cell behavior of patients with MS, a demyelinating autoimmune disease mediated by Th1 and Th17 cytokines. Here, 5-HT attenuated, in vitro, T-cell proliferation and Th1 and Th17 cytokines production in cell cultures from MS patients. Additionally, 5-HT reduced IFN-γ and IL-17 release by CD8 + T cells. By contrast, 5-HT increased IL-10 production by CD4 + T cells from MS patients. A more accurate analysis of these IL-10-secreting CD4 + T cells revealed that 5-HT favors the expansion of FoxP3 + CD39 + regulatory T cells (Tregs) and type 1 regulatory T cells. Notably, this neurotransmitter also elevated the frequency of Treg17 cells, a novel regulatory T-cell subset. The effect of 5-HT in upregulating CD39 + Treg and Treg17 cells was inversely correlated with the number of active brain lesions. Finally, in addition to directly reducing cytokine production by purified Th1 and Th17 cells, 5-HT enhanced in vitro Treg function. In summary, our data suggest that serotonin may play a protective role in the pathogenesis of MS., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Signalling through Toll-like receptors (TLRs) may play a role in the pathogenesis of autoimmune diseases, such as multiple sclerosis (MS). In the present study, the expression of TLR-2, -4 and -9 was significantly higher on CD4 + and CD8 + T-cells from MS patients compared to healthy individuals. Following in-vitro activation, the proportion of interleukin (IL)-17 + and IL-6 + CD4 + and CD8 + T-cells was higher in the patients. In addition, the proportion of IFN-γ-secreting TLR + CD8 + T-cells was increased in MS patients. Among different IL-17 + T-cell phenotypes, the proportion of IL-17 + TLR + CD4 + and CD8 + T-cells producing IFN-γ or IL-6 were positively associated with the number of active brain lesions and neurological disabilities. Interestingly, activation of purified CD4 + and CD8 + T-cells with ligands for TLR-2 (Pam3Csk4), TLR-4 [lipopolysaccharide (LPS)] and TLR-9 [oligodeoxynucleotide (ODN)] directly induced cytokine production in MS patients. Among the pathogen-associated molecular patterns (PAMPs), Pam3Csk4 was more potent than other TLR ligands in inducing the production of all proinflammatory cytokines. Furthermore, IL-6, IFN-γ, IL-17 and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels produced by Pam3Csk4-activated CD4 + cells were directly associated with disease activity. A similar correlation was observed with regard to IL-17 levels released by Pam3Csk4-stimulated CD8 + T-cells and clinical parameters. In conclusion, our data suggest that the expansion of different T helper type 17 (Th17) phenotypes expressing TLR-2, -4 and -9 is associated with MS disease activity, and reveals a preferential ability of TLR-2 ligand in directly inducing the production of cytokines related to brains lesions and neurological disabilities., (© 2017 John Wiley & Sons Ltd.)

Objective: To measure the levels of stress, anxiety, and depression of nurses working in ICUs, relating them to levels of attention before and after 24 hours., Method: An observational, quantitative, analytical study with 18 nurses undergoing an inventory of stress, anxiety, and depression, as well as assessment of attention levels and psychomotor functioning., Results: Sixty-one percent showed positive for stress. Depression was observed in 33%; and anxiety in 99.9%. A strong correlation between stress and depression (ρ = 0.564 with p <0.05) and anxiety (ρ = 1 with p <0.05) was observed. There was a weak correlation between stress and task execution time in M2 (ρ = 0.055) for TMT A, a fact that did not occur in M0 (ρ = -0.249)., Conclusion: The study shows that the workload of the nurses working in 24-hour shifts in the ICU is correlated with high levels of stress, decreases in the attention process, and psychomotor decline.

Different microbial antigens, by signaling through toll-like receptors (TLR), may contribute to Th17-mediated autoimmune diseases, such as neuromyelitis optica spectrum disorder (NMOSD). The objective of this study was to determine the proportion of different Th17-like cell subsets that express TLR in NMOSD patients. For this study, the frequency of different Th17 cell subsets expressing TLR subsets in healthy individuals (n=20) and NMOSD patients (n=20) was evaluated by cytometry. The peripheral levels of soluble CD14 (sCD14) and cytokines were determined by ELISA. Our results demonstrated that the proportion of peripheral CD4 + T cells expressing TLR2, 4 and 9 was significantly higher in NMOSD samples than in healthy subjects. In NMOSD, these cells are CD28 + PD-1 - CD57 - and produce elevated levels of IL-17. Among different TLRs + Th17-like subsets, the proportion of those that co-express IL-17 and IL-6 was significantly higher in NMOSD patients, which was positively correlated with sCD14 levels and EDSS score. By contrast, the percentage of TLRs + Treg17 cells (IL-10 + IL-17 + ) was negatively related to sCD14 and the severity of NMOSD. In conclusion, the expansion of peripheral IL-6-producing TLR + Th17-like cells in NMOSD patients was associated with both bacterial translocation and disease severity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pregnancy favors antibody production, and some evidence has suggested a direct effect of estrogen on B cells. The impact of pregnancy on circulating follicular helper T (T FH ) cells, typically identified by the expression of CD45RO and CXCR5, has not been previously investigated. Here, the percentage of T FH cells, co-expressing or not PD-1, ICOS, or CXCR3 markers was significantly higher in pregnant women (PW) as compared with non-pregnant ones (nPW). Furthermore, the percentage of CXCR3 + T FH cells able to produce IL-6, IL-21, and IL-10 was significantly higher in PW than nPW. Interestingly, anti-CMV and anti-HBs antibody titers were significantly higher in the plasma of PW and were directly correlated with IL-21-producing CXCR3 + T FH cells. Finally, peripheral estrogen levels, but not progesterone, were positively related to either PD-1 + CXCR3 + T FH cells or plasma anti-CMV and anti-HBs IgG antibodies. In summary, our data suggests a positive effect of pregnancy on the proportion of CD4 + T cell subset specialized in helping B cells. This phenomenon, which could be related to the high estrogen levels produced during pregnancy, may help to explain why pregnancy favor humoral immunity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Studies have suggested the pivotal role of T helper type 1 (Th1) -related cytokines on the outcome of hepatitis C virus (HCV) infection. Nevertheless, the role of different interleukin-17 (IL-17) -secreting T cells on chronic hepatitis C (CHC) is less clear. Here, the in vivo IL-1β, IL-6, and IL-17 levels were positively correlated with both alanine transaminase (ALT) levels and hepatic lesions. When compared with the control group, CHC patients showed a lower proportion of IL-17-secreting (CD4 + and CD8 + ) T cells capable of simultaneously producing IL-21. Moreover, the percentage of IL-10-secreting Th17 cells was also lower in CHC patients. Notably, advanced liver lesions were observed among those patients with lower percentage levels of IL-17-producing T cells positive for IL-21, interferon-γ (IFN-γ) and IL-10. In contrast, the severity of hepatic damage was associated with peripheral single IL-17 + T cells. The percentage of IL-17 + IL-21 - IFN-γ + (CD4 + and CD8 + ) T-cell phenotypes was positively associated with plasma CD14 levels. Finally, elevated levels of circulating CD14 were detected among CHC patients with extensive liver damage. In summary, although preliminary, our results suggest that a balance between different IL-17-producing T cells, associated with peripheral levels of CD14, may be a progress marker for liver disease in chronically HCV-infected patients., (© 2017 John Wiley & Sons Ltd.)

Fatigue is a common and disabling symptom of multiple sclerosis (MS), a classical Th1- and Th17-mediated autoimmune disease. There is no effective pharmacological treatment for fatigue, but some reports point towards beneficial effects of physical activity on management of the fatigue in MS patients. As both MS and fatigue have been associated with dysregulated cytokine network production, the objective of the present study was to evaluate the impact of a physical activity program consisting of a 12-week series of combining Pilates and aerobic exercises on fatigue severity, determined by FSS, and cytokine production, quantified by ELISA, by T cells from MS patients (n=08) with low disability (EDSS≤2). The results showed decrease in FSSs in all patients at the end of physical activity intervention. Regarding the cytokines, a significant reduction of IL-22 release was observed in polyclonally-activated T cells form MS patients post-training follow-up. Interestingly, while the physical activity attenuated the ability of dopamine in up-regulating Th17-related cytokines, it enhanced the anti-inflammatory effects of serotonin, evidenced by high IL-10 production. In summary, all results suggest that programmed physical activity has beneficial effects on management of fatigue in MS patients, and it could be related, at least in part, to its ability in regulating neuroimmune parameters into T cell compartment., (Copyright © 2016 Elsevier B.V. All rights reserved.)