Development of asthmatic response upon bronchial allergen challenge is associated with dynamic changes of interleukin-10-producing and interleukin-10-responding CD4+ T cells.

The role of adaptive immune system in regulation of asthmatic responses remains elusive. Here, we performed a comprehensive time-course analysis of mutual relationships between development of asthmatic response following allergen challenge and changes in several CD4+ T cell subsets which we characterized as either releasing interleukin-10 (CD4+CD25-CD127- and CD4+CD25+CD127+ T cells) or responding to IL-10 (CD4+ T cell subsets expressing CD210). Patients that developed asthmatic reaction were described as responders (R) whereas the others were named non-responders (NR). In R, in contrast to NR, at 6 h, we demonstrated significant expansion of CD4+CD25-CD127- T cells which was followed by drop to baseline values at 24 h. In contrast, in R, we observed decrease in numbers of CD4+CD25+CD127+ and CD4+CD25-CD127+ T cells at 24 h. Interestingly, at baseline, despite comparable IL-10 levels, R presented with lower levels of all CD4+ T cell subsets expressing CD210. In R, the numbers of CD4+CD210+ T cell subsets were further decreased following bronchial challenge which was paralleled by decrease in IL-10 serum levels. Altogether, our data suggest that dynamic interactions between IL-10-producing and IL-10-responding CD4+ T cells could contribute to pathogenesis of asthmatic responses in atopic individuals.

Delayed diagnosis of human immunodeficiency virus infection in a patient with non-specific neurological symptoms and pancytopenia: a case report.

INTRODUCTION: Both non-specific presentation and asymptomatic course of human immunodeficiency virus infection lead to undiagnosed long-term persistence of the virus in a patient's organism. CASE PRESENTATION: Here, we present a case of a 31-year-old Caucasian man with non-specific neurological symptoms and pancytopenia, who was referred to an internal medicine ward for further diagnosis. Upon admission to our hospital, he denied any past risky behaviors and refused to have his blood collected for human immunodeficiency virus testing. Later, he eventually provided consent to conduct the human immunodeficiency virus test which turned out to have a positive result. The overall clinical pattern indicated an advanced-stage of acquired immunodeficiency syndrome, which contrasted with the history he had provided. CONCLUSIONS: This case report indicates the need to consider human immunodeficiency virus/acquired immunodeficiency syndrome diagnosis in patients with non-specific neurological and hematological disorders. Our report also demonstrates difficulties that can be experienced by the physician while trying to obtain both a clear history and consent to perform human immunodeficiency virus testing.

Decreased CD127 expression on CD4+ T-cells and elevated frequencies of CD4+CD25+CD127- T-cells in children with long-lasting type 1 diabetes.

Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127- phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127- T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127- T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25- T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127- T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype.

Phenotypic correlations between monocytes and CD4+ T cells in allergic patients.

Despite widely acknowledged contributions of innate and adaptive immune systems to the pathogenesis of allergic diseases, mutual interactions occurring in vivo between components of those two systems have not been studied in sufficient detail. Here, we wished to investigate whether phenotypic features of monocytes and CD4+ T cells in allergic patients are reciprocally related. Therefore, we recruited 50 untreated house dust mite-sensitive allergic rhinitis patients and 29 non-atopic healthy individuals and performed comprehensive simultaneous flow cytometric analysis of mutual correlations between levels of CD14, CD16, CD163, CD206, CD124 (IL-4R), CD210 (IL-10R) and CD25, CD124, CD127 (IL-7R), CD210, ICOS expression on monocytes and CD4+ T cells, respectively. We found that CD163 monocyte expression in allergic but not healthy subjects is positively correlated with monocyte IL-10R, and, to a lesser extent, CD206, but not IL-4R expression. Levels of CD163 expression were not related to frequencies of CD14++CD16-, CD14++CD16+, and CD14+CD16++ monocyte subsets. In contrast to healthy controls, intensities of monocyte IL-10R in allergic individuals were significantly correlated with monocyte CD206 and IL-4R expression. In addition, levels of monocyte IL-4R and IL-10R monocyte expression were positively correlated to expression of IL-4R and IL-10R on CD4+ T cells in both groups of studied subjects. Interestingly, we demonstrated a significant positive correlation between levels of monocyte CD206 expression and levels of IL-10R and IL-4R expression on CD4+ T cells in allergic but not healthy individuals. In summary, we conclude that allergic rhinitis is associated with a number of phenotypic alterations of circulating monocytes and CD4+ T cells.

Relationship between circulating endothelial progenitor cells and endothelial dysfunction in children with type 1 diabetes: a novel paradigm of early atherosclerosis in high-risk young patients.

OBJECTIVE: The low number of circulating endothelial progenitor cells (EPCs) has emerged as a biomarker of cardiovascular (CV) risk in adults. Data regarding EPCs in paediatric populations with CV risk factors are limited. The aim of the study was to estimate the EPC number and its relationship with vascular function and structure in children with type 1 diabetes mellitus (T1DM). DESIGN AND METHODS: We performed a comparative analysis of 52 children with T1DM (mean age 14.5 years; diabetes duration, 6.0 years; HbA1c level, 8.5%) and 36 healthy age- and gender-matched control children. EPCs were identified and analysed by flow cytometry with the use of MABs directed against CD34, CD144 (VE-cadherin) and CD309 (VEGFR-2). sICAM-1, hsCRP, thrombomodulin and adiponectin levels were also assessed. We evaluated vascular function (flow-mediated dilation (FMD)) and structure (carotid intima-media thickness (IMT)) ultrasonographically. RESULTS: Frequencies of CD34+ cells were similar in both groups (P=0.30). In contrast, frequencies of CD34+VE-cadherin+ cells were significantly higher in diabetic children compared with the healthy group (P=0.003). Similarly, diabetic patients tended to present with higher frequencies of CD34+VEGFR+ cells (P=0.06). FMD was lower (6.9 vs 10.5%, P=0.002) and IMT was higher (0.50 vs 0.44 mm, P=0.0006) in diabetic children. We demonstrated a significant relationship between CD34+VEGFR-2+ cells and BMI (r=0.3, P=0.014), HDL (r=-0.27, P=0.04), sICAM-1 (r=0.47, P=0.023) and FMD (r=-0.45, P<0.001). Similarly, frequencies of CD34+VE-cadherin+ cells were significantly correlated with BMI (r=0.32, P=0.02) and FMD (r=-0.31, P=0.03). CONCLUSIONS: We demonstrated here that increased frequencies of EPCs observed in diabetic children are negatively correlated with endothelial function. Further studies are warranted to assess whether this phenomenon might result from effective mobilisation of EPCs in order to repair damaged endothelium in children at increased risk for atherosclerosis.

[Evaluation of CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in the peripheral blood of young patients with Hashimoto's thyroiditis and Graves' disease]. / Analiza komórek CD4+CD161+CD196+ i CD4+IL-17+ Th17 we krwi obwodowej u mlodocianych z zapaleniem tarczycy typu Hashimoto i choroba Gravesa-Basedowa.

INTRODUCTION: Up till now, altered balance of Th1 and Th2 immune cells has been postulated to play an important role in the pathogenesis of autoimmune thyroid diseases (AITD). However, recent studies on thyroid diseases suggest a new role for Th17 (T helper 17) cells that have been classified as a new lineage, distinct from Th1, Th2 and Treg cells. Despite wide interest, the role of Th17 cells in the pathogenesis of inflammatory and autoimmune diseases is still being debated. Th17 cells are involved in immune responses against extracellular pathogens and have the ability to secrete cytokines: IL-17, IL-17F, IL-22 and IL-21. Th17 cells can be characterized by several surface markers, i.e. CCR6 (CD196), IL-23R, IL-12Rbeta2 and CD161. AIM OF THE STUDY: Was to estimate the frequencies of circulating CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in patients with Graves' disease (GD, n=20, mean age ± SEM 14.9 ± 6 years), Hashimoto's thyroiditis (HT, n=20, mean age ± SEM 15.2±3 yrs) and in healthy controls (C, n=20, mean age ± SEM 15.4 ± 2 yrs). MATERIAL AND METHODS: Polychromatic flow cytometry and several fluorochrome-conjugated monoclonal antibodies were applied to delineate Th17 cells with either CD4+CD161+CD196+ or CD4+IL-17+ phenotype using apparatus FACSCalibur (BD Biosciences). Thyroid anti-TSH receptor immunoglobulins (TRAK), anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies were measured in all the samples using electrochemiluminescence "ECLIA" with Modular Analytics E170 analyzer (Roche Diagnostics, Poland). RESULTS: In untreated HT children we observed an increased percentage of CD4+CD161+CD196+ (7.1 ± 3.5 vs. 3.7 ± 1.8; p <0.04) and CD4+IL-17+ (3.7 ± 2.7 vs. 1.4±0.4; p <0.01) Th17 lymphocytes in comparison to the healthy controls. In untreated and treated GD children we did not reveal such abnormalities in the population of these cells compared to the controls. In cases with HT, a positive correlation between the percentage of CD4+IL-17+ and CD4+CD161+CD196+ T cells and serum level of anti-TPO antibodies (r=0.48; p <0.025; r=0.65; p <0.01; respectively) was detected. CONCLUSIONS: We conclude that the increased percentage of Th17 cells in children with untreated Hashimoto's thyroiditis can suggest their role in initiation and development of immune and inflammatory processes in this endocrinopathy.