RESUMEN
BACKGROUND: Immunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking. OBJECTIVES: As part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age. METHODS: Immunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25(bright) and FoxP3(+) expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated. RESULTS: The proportion of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25(+)T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4(+)CD25(bright) cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25(+)T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4(+)CD25(+) FoxP3(+) T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4(+)CD25(+) IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4(+)CD25(+)FoxP3(+)T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Hipersensibilidad/inmunología , Subgrupos de Linfocitos T/inmunología , Separación Celular , Preescolar , Citocinas/biosíntesis , Citocinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/inmunología , Humanos , Hipersensibilidad/epidemiología , Lactante , Recién Nacido , Subunidad alfa del Receptor de Interleucina-2/inmunología , Estudios Longitudinales , Masculino , Fenotipo , Población UrbanaRESUMEN
An in vitro model Ebola infection was used to study the humoral response of human mononuclear cells to stimulation by purified inactivated Ebola virus antigen. Inactivated Ebola virus was cocultivated with human mononuclear cells in the presence or absence of B-cell mitogen LPS E. coli: B5. An increase in the rate of synthesis of immunoglobulins (both IgG and, to a less extent, other classes) was observed. The Ebola virus proteins were suggested to exert no suppression effect on B-cells. The IgM/IgG synthesis was evaluated by EIA in supernatants after 7 days of cultivation. It was concluded that Ebola fever is accompanied by active humoral immune response, which provides a promising basis for further search of the methods of treatment of this disease.
Asunto(s)
Anticuerpos Antivirales/biosíntesis , Antígenos Virales/inmunología , Ebolavirus/inmunología , Leucocitos Mononucleares/virología , Anticuerpos Antivirales/análisis , Antígenos Virales/farmacología , Células Cultivadas , Humanos , Técnicas para Inmunoenzimas , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Leucocitos Mononucleares/inmunología , Factores de TiempoRESUMEN
An in vitro model infection caused by Ebola virus (EV) showed a high production of tumor necrosis factor-alpha by human peripheral lymphocytes concurrently with a simultaneous reduction in the synthesis of interleukin-1 in response EV antigen stimulation. This may be an important factor in that VE suppresses the body's immunological resistance, which in turn causes unterferon deficiency and suppresses the formation of T helper cells.
Asunto(s)
Antígenos Virales/inmunología , División Celular/inmunología , Ebolavirus/inmunología , Interleucina-1/biosíntesis , Linfocitos T Colaboradores-Inductores/citología , Factor de Necrosis Tumoral alfa/biosíntesis , Humanos , Técnicas In Vitro , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismoAsunto(s)
Expresión Génica , Interleucina-1/genética , Interleucina-6/genética , Esclerosis Múltiple/inmunología , Proteínas de Neoplasias , ARN Mensajero , Proteínas de los Retroviridae/inmunología , Factor de Necrosis Tumoral alfa/genética , Proteínas del Envoltorio Viral/inmunología , Adulto , Anciano , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Femenino , Humanos , Interleucina-1/inmunología , Interleucina-6/inmunología , Leucocitos Mononucleares/clasificación , Leucocitos Mononucleares/citología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Ebola virus (EV), an extremely infectious pathogen, causes severe hemorrhagic fever in humans and nonhuman primates. The disease pattern includes damage of parenchymal cells of vital organs in association with hemostatic and immune disorders. Vaccination with the inactivated virions does not provide an effective immune protection against the disease. The inadequate immune response may be directly caused by the virus, and, hence, it may presumably be crucial in the pathogenic process and prophylactic treatment of Ebola infection. The suggested immunosuppressive properties of EV were examined in this study. We have demonstrated that the whole heat-inactivated virions can dose-dependently suppress human lymphocyte mitogen-stimulated proliferation in vitro. In further analyses, we identified the viral protein responsible for the suppressive effect, and we showed that it was provided by a protein corresponding to a 125-kDa envelope glycoprotein (GP-125). The protein alone inhibited lymphocyte proliferation, whereas the other viral proteins were without significant effect on blastogenesis. To determine the immunosuppressive properties of different portions of GP-125, deletion mutants of GP were designed based on predicted localisation of antigen sites. They were expressed as recombinant proteins and studied in proliferation assays. We identified a 40-amino acid sequence at the N-terminus of GP-125 that exerted a suppressive effect on blastogenesis.
Asunto(s)
Ebolavirus/inmunología , Inmunosupresores/farmacología , Activación de Linfocitos/efectos de los fármacos , Linfocitos T/inmunología , Proteínas del Envoltorio Viral/farmacología , Ebolavirus/patogenicidad , Humanos , Mutación , Eliminación de Secuencia , Proteínas del Envoltorio Viral/genéticaRESUMEN
It was shown that in vivo trecrezan possessed strong immunoactive properties: it decreased the spot-forming activity of polypotent stem blood cells, stimulated lympho- and hemopoesis, antibody formation, possessed steady antiinflammatory activity. It stimulated in vitro mononuclear cell proliferation in man due to its direct action on B lymphocytes and increase in lymphokine and monokine production.