Allergic conjunctivitis (AC) is one of the most common eye disorders in ophthalmology. In mice models, it has been suggested that control of allergic conjunctivitis is a delicate balance between Tregs and inflammatory migrating effector cells. Our aim was to evaluate the frequency of Tregs and the frequency of homing receptors expressing cells in peripheral blood mononuclear cells (PBMC) from patients with perennial allergic conjunctivitis (PAC). The analyses of phenotypic markers on CD4+ T cells and both soluble or intracellular cytokines were performed by flow cytometry. CD4+CD25+ cells were 15 times more frequent in PBMC from patients than HC; the vast majority of these CD4+CD25+ cells were FOXP3−, and most of CD4+ T cells were CCR4+ and CCR9+ cells. Upon allergen-stimulation, no significant changes were observed in frequency of Treg; however, an increased frequency of CD4+CCR4+CCR9+ cells, CD4+CD103+ cells and CD4+CD108+ cells with increased IL-5, IL-6, and IL-8 production was observed. These findings suggest an immune dysregulation in PAC, characterized by diminished frequency of Tregs and increased frequency of circulating activated CD4+ T cells; upon allergen-stimulation, these cells were expressing cell-surface molecules related to mucosa homing and were able to trigger an inflammatory microenvironment.

Background: Dialyzable leukocyte extracts (DLE) are heterogeneous mixtures of peptides less than 10 kDa in size that are used as immunomodulatory adjuvants in immune-mediated diseases. Transferon TM is DLE manufactured by National Polytechnic Institute (IPN), and is registered by Mexican health-regulatory authorities as an immunomodulatory drug and commercialized nationally. The proposed mechanism of action of Transferon TM is induction of a Th1 immunoregulatory response. Despite that it is widely used, to date there are no reports of adverse events related to the clinical safety of human DLE or Transferon TM. Objective: To assess the safety of Transferon TM in a large group of patients exposed to DLE as adjuvant treatment. Methods: We included in this study 3844 patients from our Clinical Immunology Service at the Unit of External Services and Clinical Research (USEIC), IPN. Analysis was performed from January 2014 to November 2014, searching for clinical adverse events in patients with immune-mediated diseases and treated with * Corresponding author. Transferon TM as an adjuvant. Results: In this work we observed clinical nonserious adverse events (AE) in 1.9% of patients treated with Transferon TM (MD 1.9, IQR 1.7-2.0). AE were 2.8 times more frequently observed in female than in male patients. The most common AE were headache in 15.7%, followed by rash in 11.4%, increased disease-related symptomatology in 10%, rhinorrhea in 7.1%, cough in 5.7%, and fatigue in 5.7% of patients with AE. 63% of adverse event presentation occurred from day 1 to day 4 of treatment with Transferon TM , and mean time resolution of adverse events was 14 days. In 23 cases, the therapy was stopped because of adverse events and no serious adverse events were observed in this study. Conclusion: Transferon TM induced low frequency of nonserious adverse events during adjuvant treatment. Further monitoring is advisable for different age and disease groups of patients.

Background: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, with an increasing incidence in clinical practice. AD models have demonstrated that TGF-β signaling is compromised in regulatory T cells (Tregs). Objectives: This study aimed to investigate the TGFβ-dependent in vitro conversion of CD4 + CD25 -T cells derived from AD-patients into CD4 + CD25 + Foxp3 + induced Tregs (iTregs) in comparison to healthy controls. Methods: To analyze in vitro iTreg conversion, human CD4 + CD25 -T cells were cultured on anti-CD3-coated plates in the presence of TGF-β and IL-2 for up to 3 days. Consequently, the underlying mechanism of impaired CD4 + CD25 + Foxp3 + iTreg generation was explored by focusing on TGF-β signaling. Finally, the functionality of iTregs was investigated. Results: Conversion of CD4 + CD25 -Foxp3into CD4 + CD25 + Foxp3 + iTregs was diminished in AD individuals. Impaired iTreg generation was accompanied by a reduced surface expression of GARP (glycoprotein A repetitions predominant), a marker for activated Tregs. A reduced expression of Smad3 mRNA was revealed in CD4 + CD25 -T cells. Interestingly, the sup-pressive quality of iTregs was found to be equal in cells derived from AD and healthy donors. Conclusion: The signaling effect of TGF-β receptors on the suppressor quality of iTreg conversion is conserved. Impaired iTreg generation might be a reason for the lack of immune suppression in AD patients and contributes to the chronicity of the disease.

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BackgroundIt is well known involvement of CD4+ T cells in the maintenance of allergic immune response at conjunctiva; recently, it was suggested in the mouse model that γδ T cells are needed for the ocular allergic response maintenance; however contribution of γδ T cells in human allergic conjunctivitis is still unknown. The aim of this study was to evaluate the frequency of γδ T cells in AC patients.MethodsPatients with AC diagnosis were included. All participants gave their informed consent for blood sampling after written information was provided. Peripheral blood mononuclear cells (PBMC) were separated on a Ficoll density gradient, after that PBMC were stained with mAb against human CD3-PeCy5 and γδ-PE. The cells were analysed for marker expression by collecting 10,000 events using a FACScan flow cytometer (Becton Dickinson, CA, USA) and CellQuest Pro software. To analyse cell surface marker staining, a gate was drawn around the lymphocyte population based on their physical properties (forward and side scatter). Data were analyzed with t test and differences were considered statistically significant with P < 0.05.ResultsWe observed a higher frequency of gd T cells in patients with AC, gd T cells were increased 11.9 times in AC-patients (22.63 ± 2.9%) than healthy donors (1.9 ± 1.9%) (P = 0.002).Conclusionsγδ T cells are increased in allergic conjunctivitis patients. These data suggest that lipids antigens could be involved in pathogenesis of allergic conjunctivitis in humans and possibly implicated in chronic responses at ocular level, as has been suggested in the mouse model of allergic conjunctivitis.