Characterizing T cell subsets in the nasal mucosa of children with acute respiratory symptoms (original) (raw)

Peripheral immune cell markers in children with recurrent respiratory infections in the absence of primary immunodeficiency

Experimental and Therapeutic Medicine, 2019

The immune system of a child has a degree of immaturity that is maintained until 6-7 years of age. Immaturity may be due to age-related functional disorders in the immune response. A healthy child can contract a series of infections which contribute to the maturation of the immune system during the pre-pubertal period. If repeated infections with prolonged or severe complications occur during childhood, the presence of an immunodeficiency should then be considered. Much more frequent than primary immunodeficiency are recurrent infections (frequently involving the upper respiratory tract), which are less severe and occur under the conditions of an immune system with no apparent major defects. A child can present with 4 to 8 episodes of respiratory infections within a year, during the first 5 years of its life. The average duration of infection is 8 days and up to 2 weeks; if the child presents with 3 episodes of acute infections over a period of 6 months, the respiratory infections are then considered recurrent. The aim of this study was to identify the immunological changes or deviations that cause this clinical syndrome in children. For this purpose, 30 children with recurrent respiratory infections and 10 healthy children were included. Immunoglobulin levels were examined and immunophenotyping was performed. We found that the serum immunoglobulin levels were in the normal range in 70% of the children. On the contrary, our data revealed changes in peripheral cell populations, the most important being the decrease in the T-cluster of differentiation (CD)8 + and total B cell percentages and the increase in the number of memory B cells. The data obtained herein indicated that the decrease in the number of total B cells was mainly due to the decrease in the number of naive IgD + B cells. On the whole, the findings of this study indicate that recurrent respiratory infections may be associated with an altered cellular immune response. In such situations, the investigation of immunological parameters, such as T and B cell subtypes could complete the clinical diagnosis and guide the treatment strategy, thus increasing the quality of life of patients.

Dynamics of Human Respiratory Virus-Specific CD8+ T Cell Responses in Blood and Airways during Episodes of Common Cold

The Journal of Immunology, 2008

We determined the dynamics of CD8 ؉ T cells specific for influenza virus and respiratory syncytial virus in blood and tracheostoma aspirates of children during the course of respiratory infections. We showed that during localized respiratory infections the ratio of activated effector CD8 ؉ T cells to resting memory/naive CD8 ؉ T cells in peripheral blood increased significantly. Furthermore, the number of effector/memory T cells specific for respiratory viruses declined in blood and increased in the airways, suggesting that these T

Characterisation of bronchus-associated lymphoid tissue and antigen-presenting cells in central airway mucosa of children

Thorax, 2010

Background Childhood represents an immunological window of vulnerability in which individuals are at increased risk for both serious infections and development of allergic diseases, particularly affecting the airways. However, little is known about how the airway mucosal immune system is organised and functions during early age. Here, the organisation of immune cells in bronchial mucosa of children was characterised. Methods Immunophenotyping was performed on mucosal samples obtained postmortem from nine children aged 2e15 years without any history of atopic manifestations or any signs of respiratory disease, who died from non-inflammatory causes. Results In all nine cases, isolated lymphoid follicles (ILFs), interpreted as bronchus-associated lymphoid tissue (BALT), were found, constituting an average frequency of 60 ILFs/cm 2 of airway mucosal surface. Outside these ILFs, dense networks of CD11c + myeloid dendritic cells (DCs), CD68 + macrophages and CD3 + CD45RA À memory T cells were found. Plasmacytoid DCs occurred in low numbers. Importantly, intraepithelial antigen-presenting cells were found to extend cellular projections into the airway lumen. Conclusion The density and location of antigenpresenting cells and T cells in this age group are similar to those observed in adults. However, in contrast to adults, BALT appears to be a normal feature of the airway mucosa throughout childhood, suggesting that these structures contribute to regional immunity and homeostasis. This indicates that the local immune system in the airways of children has unique features which should be taken into account, not only when studying airway immunology and immunopathology, but also in the development of mucosal vaccines.

T cell cytokine profiles in childhood asthma

Thorax, 2003

Background: An imbalance of T cell subsets in asthma with a predominance of Th2 type cells has been proposed. The aim of this study was simultaneously to detect surface markers and intracellular production of cytokines in T cells from the airways of children with and without asthma. Methods: Bronchoalveolar lavage (BAL) fluid was obtained by wedging a suction catheter into the distal airway immediately before elective surgery. Cells were stimulated with phorbol 12-myristrate 13-acetate (PMA) and ionomycin and intracytoplasmic cytokine retention was achieved using monensin. The cells were stained with the relevant antibodies and analysed by flow cytometry. Results: No statistical difference was observed between children with atopic asthma, atopic non-asthmatic subjects, and normal controls in the percentage of CD3+ cells producing interleukin (IL)-2 or IL-4. Interferon (IFN)γ+ T cells were, however, present in a much higher percentage than either IL-2 or IL-4 positive cells. The perc...

Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections

The Journal of Immunology, 2003

Previous studies have shown that heterologous viral infections have a significant impact on pre-existing memory T cell populations in secondary lymphoid organs through a combination of cross-reactive and bystander effects. However, the impact of heterologous viral infections on effector/memory T cells in peripheral sites is not well understood. In this study, we have analyzed the impact of a heterologous influenza virus infection on Sendai virus-specific CD8 ؉ effector/memory cells present in the lung airways. The data show a transient increase in the numbers of Sendai virus nucleoprotein 324 -332/K b -specific CD8 ؉ memory T cells in the airways of the influenza-infected mice peaking around day 4 postinfection. Intratracheal transfer studies and 5-bromo-2-deoxyuridine incorporation demonstrate that this increase is due to the recruitment of resting memory cells into the airways. In addition, the data show that these immigrating memory cells are phenotypically distinct from the resident memory T cells of the lung airways. A similar influx of nonproliferating Sendai virus nucleoprotein 324 -332/K b -specific CD8 ؉ memory T cells is also induced by a secondary (homologous) infection with Sendai virus. Together, these data suggest that inflammation can accelerate memory T cell migration to nonlymphoid tissues and is a part of the normal recall response during respiratory infections.

Dynamic changes in innate immune and T cell function and composition at the nasal mucosa across the human lifespan

The very young and very old are at increased risk of serious infections, including pneumonia. This may relate to changes in the immune system as young children have limited immunological memory, while immunosenescence, inflammaging and a decreased pool of naive immune cells are described with advanced age. How the immune system changes with age at mucosal surfaces, from where infections frequently develop, is not very clear as access to human tissue samples is limited. Therefore, we aimed to assess the composition and activation state of the immune system at the human mucosa. Here, we profiled nasal immune cells from 207 individuals between 1 to 80 years old using flow cytometry. Neutrophil and monocyte functionality were measured using whole blood assays. Levels of thirty nasal cytokines were measured from nasal lining fluid. Nasopharyngeal colonization by Streptococcus pneumoniae was assessed using classical microbiology and associated with immune responses. We found that young ch...