RESUMEN
CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.
Asunto(s)
Presentación de Antígeno/inmunología , ADN/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Linfocitos T/inmunología , Animales , Presentación de Antígeno/genética , Línea Celular , ADN/genética , Humanos , Tolerancia Inmunológica , Oligonucleótidos , Péptidos , Unión ProteicaRESUMEN
OBJECTIVE: To demonstrate the involvement of T lymphocytes reactive to autoantigens in the pathogenesis of autoimmune diseases and to analyse their clinical relevance. METHODS: The frequency of T cell clones reactive to double strand DNA (dsDNA), Nucleohistone (NH) complex and Dnase I was calculated for the peripheral blood mononuclear cells (PBMC) of 15 SLE patients and 9 healthy subjects by proliferation assay. RESULTS: DsDNA- and NH-specific T cell clones were found in the majority of the patients analysed (frequency ranging from 2 to 50 clones/10(7) PBMC), while their absence or very low frequency (2 clones/10(7) PBMC) was observed in the control PBMC. Their frequency significantly correlated with decreased serum concentrations of C3 and C4 and with the systemic lupus erythematosus disease activity index (P = 0.03). A very low frequency of Dnase I-reactive T cell clones was observed in both SLE and healthy subjects. CONCLUSION: Our results suggest that dsDNA- and NH-reactive T lymphocytes may be involved in the pathogenesis of SLE and that their quantification in the peripheral blood of patients could be a useful tool to follow the clinical course of the disease.
Asunto(s)
Enfermedades Autoinmunes/etiología , Autoinmunidad , Lupus Eritematoso Sistémico/etiología , Linfocitos T/inmunología , Adulto , División Celular , Línea Celular , Células Clonales , ADN/inmunología , Desoxirribonucleasas/inmunología , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Histonas/inmunología , Humanos , Inmunidad Celular , Leucocitos Mononucleares/inmunología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Persona de Mediana EdadAsunto(s)
Autoantígenos/inmunología , ADN/inmunología , Lupus Eritematoso Sistémico/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Linfocitos T/inmunología , Células Clonales , Reordenamiento Génico de la Cadena beta de los Receptores de Antígenos de los Linfocitos T , Humanos , Lupus Eritematoso Sistémico/patología , Linfocitos T/patologíaRESUMEN
During eighteen orthopedic surgery operation on the cervical spine (C4-D1) we could verify that the moderate hemodilution combined with technique of anaesthesia providing for the controlled hypotension, is the only methodic with renal saving of homologous blood and absence of transfusion reaction.