RESUMEN
Systemic lupus erythematosus is a chronic inflammatory disease which involves multiple organs. Self-specific B and T cells play a main role in the pathogenesis of lupus and have been defined as a logical target for selective therapy. The protein annexin A1 (ANX A1) is a modulator of the immune system involving many cell types. An abnormal expression of ANX A1 was found on activated B and T cells during autoimmunity, suggesting its importance as a potential therapeutic target. We hypothesize that it may be possible to down-regulate the activity of autoreactive T and B cells from lupus patients in a humanized immunodeficient mouse model by treating them with an antibody against ANX A1. When cultured in the presence of anti-ANX A1, peripheral blood mononuclear cells (PBMC) from lupus patients showed a decreased number of immunoglobulin (Ig)G anti-dsDNA antibody-secreting plasma cells, decreased T cell proliferation and expression of activation markers and increased B and T cell apoptosis. We employed a humanized model of SLE by transferring PBMCs from lupus patients to immunodeficient non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. The humanized animals presented autoantibodies, proteinuria and immunoglobulin deposition in the renal glomeruli. Treatment of these NOD-SCID mice with an anti-ANX A1 antibody prevented appearance of anti-DNA antibodies and proteinuria, while the phosphate-buffered saline (PBS)-injected animals had high levels after the transfer. The treatment reduced the levels of autoantibodies to several autoantigens, lupus-associated cytokines and disease symptoms.
Asunto(s)
Anexina A1/inmunología , Anticuerpos/inmunología , Linfocitos B/inmunología , Modelos Animales de Enfermedad , Lupus Eritematoso Sistémico/inmunología , Linfocitos T/inmunología , Animales , Anexina A1/metabolismo , Anticuerpos/farmacología , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Activación de Linfocitos/inmunología , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismoRESUMEN
Introduction and objectives: Th17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases. Patients and methods: We included a total of 42 children: 20 with bronchial asthma (BA), 12 with cystic fibrosis (CF) and 10 healthy children without a history of allergies, aged 4-17 years. Th17 cells (CD3 + CD4 + CD161 + CCR6+) were determined in peripheral blood by flow cytometry. The concentration of serum IL-17A was measured by ELISA. Results: The BA patients had a significantly higher percentage of Th17 (12.40 ± 1.16%) compared to the CF children (7.64 ± 0.87%, p = 0.0035) and healthy (7.25 ± 0.45%, p = 0.008). Stratifying the BA group, we found higher levels of Th17 in patients with severe BA (p = 0.03), whereas patients with moderate BA had Th17 cells close to those in CF and healthy children. We found that patients with better control of BA had Th17 closer to those with CF (p = 0.98) than BA children with poor control (p<0.001) (post hoc, Bonferroni correction). CF patients with concomitant P. aeruginosa infection showed slightly higher percentages of Th17 cells than those without infection (8.08 ± 3.09% vs. 6.25 ± 2.42%, p = 0.294). Conclusions: The percentage of Th17 cells was significantly increased in the peripheral blood of children with severe BA compared to the children with moderate BA, which suggests that the former could possibly benefit from future target therapies
No disponible
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Células Th17/inmunología , Separación Celular , Citometría de Flujo , Bulgaria , Interleucina-17/sangre , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Receptores CCR6/metabolismo , Recuento de CélulasRESUMEN
INTRODUCTION AND OBJECTIVES: Th17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases. PATIENTS AND METHODS: We included a total of 42 children: 20 with bronchial asthma (BA), 12 with cystic fibrosis (CF) and 10 healthy children without a history of allergies, aged 4-17 years. Th17 cells (CD3+CD4+CD161+CCR6+) were determined in peripheral blood by flow cytometry. The concentration of serum IL-17A was measured by ELISA. RESULTS: The BA patients had a significantly higher percentage of Th17 (12.40±1.16%) compared to the CF children (7.64±0.87%, p=0.0035) and healthy (7.25±0.45%, p=0.008). Stratifying the BA group, we found higher levels of Th17 in patients with severe BA (p=0.03), whereas patients with moderate BA had Th17 cells close to those in CF and healthy children. We found that patients with better control of BA had Th17 closer to those with CF (p=0.98) than BA children with poor control (p<0.001) (post hoc, Bonferroni correction). CF patients with concomitant P. aeruginosa infection showed slightly higher percentages of Th17 cells than those without infection (8.08±3.09% vs. 6.25±2.42%, p=0.294). CONCLUSIONS: The percentage of Th17 cells was significantly increased in the peripheral blood of children with severe BA compared to the children with moderate BA, which suggests that the former could possibly benefit from future target therapies.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/inmunología , Células Th17/inmunología , Adolescente , Bulgaria , Recuento de Células , Separación Celular , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Interleucina-17/sangre , Masculino , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Receptores CCR6/metabolismoRESUMEN
It is well known that the increased numbers of NK cells with phenotype CD3-CD16+CD56+ can execute cytotoxic effect against trophoblast cells and might be responsible at least for a part the immune mediated reproductive failures. The aim of this study is to follow up the correlations between the increased absolute numbers of NK cells, their activation status and secretion of some cytokines in infertile patients. The results obtained clearly show that in patients with increased numbers of NK cells the percentages of HLA-DR positive NK cells were significantly higher compared to the patients with normal number of NK cells. A similar correlation was revealed when the data of blood plasma where the concentrations of IL-12 were significantly higher in patients from the first group (with increased NK cells numbers). The results from our study demonstrate that the increased numbers on CD3-CD16+CD56+ NK cells is accompanied by enhanced activation of these cells and secretion of cytokines.
Asunto(s)
Antígenos HLA-DR/genética , Infertilidad Femenina/inmunología , Interleucina-12/inmunología , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Adulto , Recuento de Células , Femenino , Antígenos HLA-DR/inmunología , Humanos , Infertilidad Femenina/genética , Interleucina-12/sangre , Persona de Mediana Edad , Regulación hacia Arriba , Adulto JovenRESUMEN
From an immunological point of view during pregnancy the interactions between the steroid sex hormones and immunocompetent cells as a part of the dynamic local and peripheral immune response is of a particular interest. The aim of our study is to investigate the expression of the early activation marker CD69 in T-lymphocytes subpopulation: CD4+ and CD8+ in peripheral blood from pregnant and non-pregnant women. Our data clearly demonstrate an increase of the percentage of activated CD4+ lymphocytes in pregnant women in comparison to non-pregnant and this difference is statistically significant. A similar but not statistically significant dependency is observed in CD8+ and CD69+ lymphocytes. From the obtained results we conclude that during pregnancy the activation of CD4+ lymphocytes is increased, which probably leads to an increased production of cytokines that shifts the immune response to Th2 type which is protective for pregnancy. This could be partly due to the increased levels of progesterone.