IMMUNOLOGICAL MARKERS OF CHILDREN HEALTH PROBLEMS LIVING IN THE CONDITIONS OF ATMOSPHERIC AIR POLLUTION BY ALUMINUM

We analyzed the characteristics of the immunoregulatory parameters of the child population (94 people) aged 5 to 10 years exposed to aluminum. The control group included 45 children, matched by age and sex, living in areas not exposed to aluminum. The study consisted of determining the content of IgG specific to aluminum, total IgE (hypersensitivity indicators) and phagocytic-active cells. A study of CD-markers of cell differentiation and intracellular markers for assessing the apoptosis system (absolute and relative suppressor T-cell receptors CD127–, Bax, anti-apoptotic protein Bcl-2 and proapoptotic cell death receptor CD95+) was performed. As a result of the research, it was reliably established that in the examined child population there are violations of the cellular immunity, which manifest themselves in a decrease in phagocytic activity by the criterion of absolute phagocytosis (42 per cent), relative phagocytosis (56 per cent) and phagocytic number (75 per cent) (for example, decrease in phagocytic activity of cells compared with control was 1.2-1.5 times), activation of absolute and relative suppressor T-cell receptors CD127–, Bax deficiency, antiapoptotic protein Bcl -2 and the proapoptotic cell death receptor CD95+ (p < 0.05) responsible for apoptosis, relative to the reference values. There is a significant increase compared with the norm of specific IgG to aluminum in 44 per cent of children of the observed group and an increase in the level of total IgE by more than 1.4 times compared to the control group (p < 0.05)

Autoimmune Cytopenias Occurring after Treatment with Chemoimmunotherapy for Non-Hodgkin Lymphomas

Autoimmune diseases, including autoimmune hemolytic anemia and immune thrombocytopenic purpura, have been described in patients with non-Hodgkin lymphoma (NHL) after immunochemotherapy. However, the underlying pathogenesis remains unclear. We examined NHL patients with autoimmune cytopenia and all patients were treated with rituximab-containing therapy. The present results showed reversed imbalances in helper/suppressor T-cell populations, and an immune system imbalance may have contributed to immunological abnormalities. Although the relationship between imbalances in helper/suppressor T-cell populations and the development of auto-antibody production after chemotherapies currently remains unclear, the immunosuppressive effects of immunochemotherapy may be a contributing factor. The long-term monitoring of T-cell populations after immunochemotherapies is important.

Antibody Light Chains Dictate the Specificity of Contact Hypersensitivity Effector Cell Suppression Mediated by Exosomes

Antibody light chains (LCs), formerly considered a waste product of immunoglobulin synthesis, are currently recognized as important players in the activation of the immune response. However, very little is known about the possible immune regulatory functions of LCs. Recently, we reported that hapten-specific LCs coat miRNA-150-carrying exosomes produced by CD8+ suppressor T cells downregulating the contact hypersensitivity (CHS) reaction in an antigen-specific manner, in mice tolerized by intravenous administration of a high dose of hapten-coupled syngeneic erythrocytes. Thus, the current studies aimed at investigating the role of hapten-specific LCs in antigen-specific, exosome-mediated suppression of CHS effector cells. Suppressor T cell-derived exosomes from tolerized B-cell-deficient µMT−/−, NKT-cell-deficient Jα18−/−, and immunoglobulin-deficient JH−/− mice were nonsuppressive, unless supplemented with LCs of specificity strictly respective to the hapten used for sensitization and CHS elicitation in mice. Thus, these observations demonstrate that B1-cell-derived LCs, coating exosomes in vivo and in vitro, actually ensure the specificity of CHS suppression. Our research findings substantially expand current understanding of the newly discovered, suppressor T cell-dependent tolerance mechanism by uncovering the function of antigen-specific LCs in exosome-mediated, cell–cell communication. This express great translational potential in designing nanocarriers for specific targeting of desired cells.

Identification and Characterization of Human Aspergillus Fumigatus-Specific Tr1-(Like) Cells

Abstract 181 Introduction: The ubiquitous mold Aspergillus fumigatus (A. fumigatus) induces two forms of pathogenesis: invasive aspergillosis in neutropenic patients and allergic aspergillosis in patients with chronic obstructive lung disease as well as in immunosuppressed patients. Mouse models of aspergillosis suggest that not only effector T cells (Teff) but also regulatory T cells (Treg) play a crucial role for the regulation of a protective T cell-mediated immunity to A. fumigatus. However, it is little-known about the involvement of Treg during A. fumigatus infection in humans. In order to develop new therapeutical strategies for the treatment of aspergillosis this project aims to understand the influence of regulatory T cells on A. fumigatus infection in humans. Material/Methods: A. fumigatus-specific CD4+ T cell clones were established from PBMC of healthy donors. Based on this clone pool Treg clones were identified due to their inability to proliferate in the absence of costimulation assessed by 3[H]-TdR incorporation as well as their Ag-specific cytokine production and phenotype determined by flow cytometry. Treg function was analyzed by their ability to suppress proliferation of autologous CD4+ T cells using CFSE dilution. Results: We identified A. fumigatus-specific T cell clones that exhibited marginal detectable proliferation after restimulation with immobilized anti-CD3 mAb in the absence of costimulation. However, these T cell clones vigorously proliferated in response to restimulation with their cognate antigen. A more detailed characterization showed that these suppressor T cell clones produced high amounts of IL-10 and moderate levels of IFN-gamma upon Ag-specific restimulation and expressed low amounts of Foxp3 but not Helios, a transcription factor that had recently been linked to natural occurring Treg. Most importantly, these T cell clones suppressed Ag-specific expansion of CD4+ Teff. This effect was contact-independent since suppression of Ag-specific CD4+ T cell expansion detected in transwell experiments was comparable to cocultures that enabled cellular-contact. Furthermore, anti-CD3/CD28-induced proliferation of naïve CD4+ T cells was not reduced in the presence of culture supernatants obtained from suppressor T cell clones after their antigen-specific restimulation in the absence of DCs. Conclusions: We identified for the first time A. fumigatus-specific CD4+ T cell clones with a Tr1(-like) IL-10+IFN-gamma+Foxp3lowHelios− phenotype. These cells suppressed expansion of A. fumigatus-specific Teff in an Ag-specific manner mediated by soluble factors released from Tr1(-like) cell clones. Since these factors did not affect CD4+ T cell proliferation in the absence of DCs our data suggest, that Tr1(-like) cell clones rather negatively regulate the stimulatory capacity of DCs leading to a reduced expansion of Ag-specific CD4+ T cells. Therefore these Tr1(-like) cells might play a protective role during A. fumigatus infection in humans. Thus, adoptive transfer of A. fumigatus-specific Treg could be useful to enhance protective immunity in patients with chronic A. fumigatus infection. Disclosures: Topp: Micromet: Consultancy, Honoraria.