RESUMO
The Island Mass Effect (IME) around the Maldives is responsible for intense blooms with distinct seasonal patterns. These blooms sustain the fishing industry of the archipelagic nation, a vital source of income that occupies about 30% of the population. Through high resolution ocean simulations, we explore the physical processes responsible for the increased productivity and its observed variability, and their sensitivity to changes in land distribution. Year-round the frictional break of the currents in the presence of shallow bathymetry produces a strong vertical shear in the flow that favors vertical mixing, independently of the currents direction. The impact of this mixing is visible at the ocean surface during March and April, when the mixed-layer is shallow and the ocean currents are generally weak. A different mechanism than observed in spring modulates the IME during the monsoon seasons, in both winter and summer, when the zonal currents forced by the strong winds cross the archipelago: the flow accelerates while squeezing between the atolls, giving rise to intense wakes, and strong upwelling originates in the lees in response to the kilometer-scale flow divergence. This upwelling creates an asymmetric cooling signal in the lee of the islands and obfuscates the effects of the enhanced vertical mixing. The land reclamation efforts being planned on some of the islands may undercut the upwelling that drives the blooms during the monsoon seasons.
RESUMO
BACKGROUND AND OBJECTIVES: The role of B cells in the pathogenic events leading to relapsing multiple sclerosis (R-MS) has only been recently elucidated. A pivotal step in defining this role has been provided by therapeutic efficacy of anti-CD20 monoclonal antibodies. Indeed, treatment with anti-CD20 can also alter number and function of other immune cells not directly expressing CD20 on their cell surface, whose activities can contribute to unknown aspects influencing therapeutic efficacy. We examined the phenotype and function of cytotoxic lymphocytes and Epstein-Barr virus (EBV)-specific immune responses in people with R-MS before and after ocrelizumab treatment. METHODS: In this prospective study, we collected blood samples from people with R-MS (n = 41) before and 6 and 12 months after initiating ocrelizumab to assess the immune phenotype and the indirect impact on cytotoxic functions of CD8+ T and NK cells. In addition, we evaluated the specific anti-EBV proliferative responses of both CD8+ T and NK lymphocytes as surrogate markers of anti-EBV activity. RESULTS: We observed that while ocrelizumab depleted circulating B cells, it also reduced the expression of activation and migratory markers on both CD8+ T and NK cells as well as their in vitro cytotoxic activity. A comparable pattern in the modulation of immune molecules by ocrelizumab was observed in cytotoxic cells even when patients with R-MS were divided into groups based on their prior disease-modifying treatment. These effects were accompanied by a significant and selective reduction of CD8+ T-cell proliferation in response to EBV antigenic peptides. DISCUSSION: Taken together, our findings suggest that ocrelizumab-while depleting B cells-affects the cytotoxic function of CD8+ and NK cells, whose reduced cross-activity against myelin antigens might also contribute to its therapeutic efficacy during MS.
Assuntos
Anticorpos Monoclonais Humanizados , Linfócitos T CD8-Positivos , Herpesvirus Humano 4 , Fatores Imunológicos , Humanos , Anticorpos Monoclonais Humanizados/farmacologia , Feminino , Adulto , Masculino , Herpesvirus Humano 4/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Pessoa de Meia-Idade , Fatores Imunológicos/farmacologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/sangue , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Estudos Prospectivos , Proliferação de Células/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Ativação Linfocitária/efeitos dos fármacosRESUMO
In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.