20 research outputs found
Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen
Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. Furthermore, adoptive transfer of pDCs before sensitization prevented disease in a mouse asthma model. On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. These studies show that pDCs provide intrinsic protection against inflammatory responses to harmless antigen. Therapies exploiting pDC function might be clinically effective in preventing the development of asthma
Bordetella pertussis pertactin knock-out strains reveal immunomodulatory properties of this virulence factor.
Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates. Knowledge on the effect that Prn deficiency has on infection and immunity to B. pertussis is crucial for the development of new strategies to control this disease. Here, we characterized the effect of Prn production by B. pertussis on human and murine dendritic cell (DC) maturation as well as in a murine model for pertussis infection. We incubated human monocyte-derived DCs (moDCs) with multiple isogenic Prn knockout (Prn-KO) and corresponding parental B. pertussis strains constructed either in laboratory reference strains with a Tohama I background or in a recently circulating clinical isolate. Results indicate that, compared to the parental strains, Prn-KO strains induced an increased production of pro-inflammatory cytokines by moDCs. This pro-inflammatory phenotype was also observed upon stimulation of murine bone marrow-derived DCs. Moreover, RNA sequencing analysis of lungs from mice infected with B. pertussis Prn-KO revealed increased expression of genes involved in cell death. These in vitro and in vivo findings indicate that B. pertussis strains which do not produce Prn induce a stronger pro-inflammatory response and increased cell death upon infection, suggesting immunomodulatory properties for Prn
IL-2 producing memory CD4(+) T lymphocytes are closely associated with the generation of IgG-secreting plasma cells
The role of specific CD4(+) T cell subsets in the induction of Immoral immune responses in humans is largely unknown. In this study, the generation of hepatitis B surface Ag-specific CD4(+) T lymphocytes following vaccination was closely monitored and characterized at the single-cell level. The appearance and absolute numbers of hepatitis B surface Ag-specific IL-2 producing effector memory CD4(+) T lymphocytes was solely and tightly related to Ab titers reached. This relation remained present many years after vaccination. Subsequently, a relation was found between Ab titers and number of IL-2 producing memory CD4(+) T lymphocytes for various other Ags. These observations matched the findings of an in vitro assay, using different T cell subsets to induce B cell differentiation into IgG-producing plasma cells. By depleting for IL-2 producing memory T cells, we demonstrated that these cells are important for B cell differentiation into IgG-producing plasma cells. Finally, blocking the action of IL-2 with an IL-2R-alpha Ab inhibited the differentiation of B lymphocytes into IgG-producing plasma cells. Based on these findings, we conclude that the development of Ag-specific IL-2-producing memory T cells appears to be essential for the development of IgG-secreting plasma cells in humans
Differential expression of TNFR1 (CD120a) and TNFR2 (CD120b) on subpopulations of human monocytes
Abstract Background Three subpopulations of monocytes can be distinguished in human blood: classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++). CD16 expressing monocytes are expanded in patients with sarcoidosis and in various other inflammatory diseases. In sarcoidosis, it is unclear whether either intermediate, nonclassical or both CD16 expressing monocytes are responsible for this increase. Data relating to the monocyte subpopulations is receiving increasing attention, but the expression of TNF receptors on these subpopulations has not been studied thus far. The aim of this study was to determine frequencies of monocyte subpopulations and their expression of TNFR1 and TNFR2 in both sarcoidosis patients and healthy controls. Methods Peripheral blood cells of sarcoidosis patients and healthy controls were stained for the markers HLA-DR, CD14, CD16, CD120a and CD120b. Cells were measured on a FACSCalibur and analyzed with FlowJo. We used Student’s t-test and a parametric One-way ANOVA for statistical analysis. Results Sarcoidosis patients had a significant higher frequency of intermediate monocytes than healthy controls. Significant differences in TNF receptor expression were found between the monocyte subpopulations, both in sarcoidosis patients as well as in healthy controls: intermediates expressed more TNFR1 than classicals and nonclassicals and nonclassicals expressed more TNFR2 than intermediates, whereas intermediates showed higher expression than classicals. Conclusions In both sarcoidosis patients and healthy controls intermediate monocytes show the highest expression level of TNFR1 among monocyte subpopulations and nonclassical monocytes show the highest expression level of TNFR2. These findings, as wells as the higher frequency of intermediate monocytes in sarcoidosis patients, provide evidence for the existence of two functionally-distinct CD16 expressing monocyte subpopulations.</p