CD4+ Th1 and Th17 responses and multifunctional CD8 T lymphocytes associated with cure or disease worsening in human visceral leishmaniasis.

Introduction: In VL, a proinflammatory phenotype is typically associated with enhanced phagocytosis and a Th1 mediated immune response resulting in infection control. In contrast, an anti-inflammatory phenotype, associated with a predominant regulatory response, typically enables intracellular multiplication of Leishmania parasites and disease progression. Methods: To investigate the impact of chemotherapy on Th2 and Th17 immune responses in patients with visceral leishmaniasis (VL), we assessed all combinations of intracellular expression of IFN-γ, IL-10, IL-4 and IL-17 in the CD4+ and CD8+ T cell populations of peripheral blood mononuclear cell (PBMC) samples from patients, after antigenic stimulation with Leishmania lysate, throughout treatment and follow-up. As increases in spleen and liver sizes and decreases in hematocrit, hemogloblin, erythrocytes, monocytes, leukocytes and platelets levels are strongly related to the disease, we studied the correlations between the frequencies of T cells producing the afore mentioned cytokines, individually and in combination, and these variables, as markers of disease or cure. Results: We found that the frequency of IFN-γ-producingCD4+ T cells increased until the end of chemotherapy with Glucantime® or AmBisome ®, while IL-10, IL-4 and IL-17-producing CD4+ T cells peaked on day 7 following the start of treatment. Although the frequency of CD4+IL-17+ cells decreased during treatment an increase was observed after clinical cure. The frequency of CD4+ T cells producing only IFN-γ or IL-17 correlated with blood monocytes levels. Frequencies of double-producers of IFN-γ and IL-10 or IL-4 correlated positively with eosinophils and platelets levels. Together, this suggest that IFN-γ drives the immune response towards Th1 at cure. In contrast, and associated with disease or Th2 response, the frequency of CD4+ IL-10+ cells correlated positively with spleen sizes and negatively with circulating monocyte levels, while the frequency of CD4+ producing both IL-4 and IL-10 correlated negatively with platelets levels. The frequency of CD8+ single-producers of IFN-γ increased from day 21 to 90 while that of single-producers of IL-10 peaked on day 7, of IL-4 on day 30 and of IL-17, on day 180. IFN-γ expression in CD8+ single- and double-producers of cytokines was indicative of an immune response associated with cure. In contrast, frequencies of CD8+ double-producers of IL-4 and IL-10, IL-4 and IL-17 and IL-10 and IL-17 and producers of three and four cytokines, were associated with disease and were low after the cure. Frequencies of CD8+ T cells producing IFN-γ alone or with IL-17 were positively correlated with platelets levels. In contrast, as markers of disease: 1) frequencies of single producers of IL-10 correlated negatively with leukocytes levels, 2) frequencies of double producers of IL-4 and IL-10 correlated negatively with platelet, leukocyte, lymphocyte and circulating monocyte levels, 3) frequencies of triple-producers of IFN-γ, IL-4 and IL-10 correlated negatively with platelet, leukocyte and neutrophil levels and 4) frequencies of producers of IFN-γ, IL-4, IL-10 and IL-17 simultaneously correlated positively with spleen size, and negatively with leukocyte and neutrophil levels. Discussion: Our results confirmed that the clinical improvement of VL patients correlates with the decrease of an IL-4 and IL-10 CD4+Th2 response, the recovery of CD4+ Th1 and Th17 responses and the frequency of CD8+ single-producers of IFN-γ and double producers of IFN-γ and IL-17.

Effects of functional and combined training on subsets of memory T cells and functional fitness of postmenopausal women: A randomized controlled trial.

This study investigated the effects of functional (FT) and combined (CT) training on memory T cells and functional fitness of postmenopausal women. 108 participants were randomly allocated to the control (CG), FT and CT groups. Functional fitness was assessed through physical tests similar to daily activities, such as dressing on and taking off a t-shirt (DTTS), 10-meter walking and countermovement jump. The CCR7 and CD45RA surface markers were used to characterize the memory T cells. Regarding the frequency of memory T cells, both training protocols reduced the percentage of CD4+ Terminally Differentiated Effector Memory T Cells Re-Expressing CD45RA (TEMRA) (FT: -38.73 %, p = 0.0455; CT: -30.43 %, p = 0.0036) and CD8+ TEMRA cells (FT: -22.24 %, p < 0.0013; CT: -13.13 %, p = 0.0051). Also, both FT and CT increased the percentage of central memory (TCM) CD4+ (FT: +55.22 %, p = 0.0104; CT: +68.03 %, p = 0.0167) and CD8+ (FT: +142.00 %, p < 0.0001; CT: +83.76 %, p = 0.0001) T cells. Furthermore, FT and CT increased the percentages of CD8+ effector memory T cells (TEM) (FT: +63.58 %, p < 0.0001; CT: +14.12 %, p = 0.0041). Regarding functional fitness, both training protocols reduced the time required to perform the DTTS (FT: -19.71 %, p < 0.0001; CT: -14.69 %, p < 0.0001) and 10-m walk tests (FT: -13.05 %, p < 0.0001; CT: -12.83 %, p < 0.0001), in addition to improving jumping ability (FT: +29.97 %, p < 0.0001; CT: +20.00 %, p < 0.0001), both compared to the pre-test or to the CG. Therefore, both FT and CT seem to be equally effective alternatives for promoting the reduction of CD4+ and CD8+ TEMRA cells, increasing the frequency of TCM and TEM cells, and improving functional fitness of postmenopausal women.

Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is a chronic and often fatal disease caused by protozoans of the genus Leishmania that affects millions of people worldwide. Patients with symptomatic VL have an impaired anti-Leishmania-specific CD4+ T-cell response, which is reversed after clinical cure. In contrast, the quality of the CD4+ and CD8+ T-cell responses involved in resistance and/or cure of VL relies on the capability of these cells to activate polyfunctional and memory responses, which are associated with the simultaneous production of three cytokines: IFN-γ, IL-2, and TNF-α. Models for the development of CD4 and CD8 T-cell quality in memory and protection to leishmaniasis have been described previously. We aimed to assess the functionality of the T cells involved in the recovery of the immune suppression throughout the VL treatment. Therefore, we cultured peripheral blood mononuclear cells (PBMCs) from VL patients and healthy controls in vitro with soluble Leishmania antigen (SLA). Cell surface markers and intracellular cytokine production were determined on days 7, 14, 21, 30, 60, 90, and 180 after the beginning of chemotherapy. We observed that the frequencies of CD4+TNF-α+IFN-γ+ and the multifunctional CD4+IL-2+TNF-α+IFN-γ+, together with CD4+TNF-α+ and CD4+IFN-γ+ T cells, increased throughout and at the end of the treatment, respectively. In addition, enhanced frequencies of CD8+IL-2+TNF-α+IFN-γ+ and CD8+TNF-α+IFN-γ T cells were also relevant in the healing process. Noteworthy, the frequencies of the CD4+ and CD8 central-memory T cells, which produce IL-2, TNF-α, and IFN-γ and ensure the memory response against parasite reinfection, are significantly enhanced in cured patients. In addition, the subset of the non-functional CD8Low population is predominant in VL untreated patients and decreases along the chemotherapy treatment. In contrast, a CD8High subset increased towards the cure. Furthermore, the cure due to treatment with meglumine antimoniate or with liposomal amphotericin B was associated with the recovery of the T-cell immune responses. We described the evolution and participation of functional T cells during the treatment of patients with VL. Our results disclosed that the clinical improvement of patients is significantly associated with the participation of the CD4+ and CD8+ cytokine-secreting T cells.

Functional and concurrent training do not impair immune function and improve functional fitness in postmenopausal women: A randomized controlled trial.

PURPOSE: To evaluate the effects of functional and concurrent training on immune function and functional fitness in postmenopausal women. MATERIALS AND METHODS: A randomized controlled trial was performed on 108 women aged 60 or older who were randomly assigned among the groups: control group (CG: n = 40; 63.88 ± 3.64 years); functional training (FT: n = 32; 63.88 ± 3.79 years); and concurrent training (CT: n = 36; 64.83 ± 4.00 years). Immune function was measured by the expression of the T-lymphocyte function-related surface markers (CD28 and CD57). Functional fitness was assessed using physical tests similar to daily activities, i.e., five times sit to stand, timed up and go, and gallon-jug shelf-transfer. RESULTS: Regarding immune function, there was only a time effect, without between-group differences. Specifically, FT and CT show a reduction and increase in CD4+ and CD8+ T cells, respectively, without impairment in the subpopulations analyzed, while CG showed a reduction in naive T cells (CD8+CD28+). For functional fitness tests, there was a time × group interaction effect for all tests, the FT and CT were superior to the CG, with FT showing differences after the fourth week, while the CT showed this effect after the eighth week of intervention. CONCLUSION: FT and CT do not impair immune function and similarly improve functional fitness in postmenopausal women. CLINICAL TRIALS REGISTRY: RBR-2d56bt.

Avaliação das necessidades dos familiares de vítimas de trauma cranioencefálico / Evaluación de necesidades de familiares de víctimas de traumatismo craneoencefálico / Evaluation of the needs of family members of traumatic brain injury patients

Objetivo identificar as necessidades dos familiares de vítimas de Trauma Cranioencefálico atendidas ambulatorialmente e o quantitativo do atendimento dessas necessidades. Método estudo descritivo de abordagem quantitativa. Foram utilizados dois instrumentos de coleta, um para caracterização do familiar e da vítima e outro, o Family Need Questionnaire, em sua versão adaptada para o português, aplicados com 22 familiares. Resultados a grande maioria (93,1%) das necessidades elencadas foi considerada "importante ou muito importante" e estão relacionadas aos subtemas "informações sobre saúde" e "suporte profissional". Conclusão as taxas de atendimentos das necessidades apontadas pelos familiares demonstram a qualidade do serviço oferecido pelos profissionais de saúde durante o tratamento e a reabilitação das vítimas de Trauma Cranioencefálico.

Objetivo identificar las necesidades de familiares de víctimas de Traumatismo Craneoencefálico atendidas en forma ambulatoria y el número de atenciones de dicha índole. Método estudio descriptivo, de abordaje cuantitativo. Fueron utilizados dos instrumentos de recolección, uno para caracterización del familiar y la víctima, y otro, el Family Needs Questionnaire, en su versión adaptada al portugués, aplicados sobre 22 familiares. Resultados la gran mayoría (93,1%) de las necesidades listadas fue considerada "importante o muy importante", y están relacionadas a los subtemas "información sobre salud" y "soporte profesional". Conclusión las cantidades de atenciones de las necesidades expresadas por los familiares demuestran la calidad del servicio ofrecido por los profesionales de salud durante el tratamiento y la rehabilitación de víctimas de Traumatismo Craneoencefálico.

Objective identify the needs of family members of traumatic brain injury patients treated in an outpatient setting and the extent of fulfillment of such needs. Method quantitative descriptive study. Two data collection instruments were used, one for characterization of the family member and patient, and the Family Needs Questionnaire, in its adapted Portuguese version, applied to 22 family members. Results most of the needs (93.1%) listed were considered "important or very important" and relate to the subthemes "health information" and "professional support." Conclusion the rates of fulfillment of needs presented by the family members show the service quality offered by the health professionals during the treatment and rehabilitation of traumatic brain injury patients.