RESUMO
Glucocorticoids (GC) are commonly used to treat inflammatory disorders such as multiple sclerosis (MS) and may exert their immunosuppressive activity by inducing apoptosis in activated lymphocytes. However, unlike relapsing-remitting MS patients, those with progressive disease respond poorly to GC treatment. The data in this communication indicate that PLP peptide-specific T cell clones from progressive, but not relapsing-remitting MS patients are resistant to GC-induced apoptosis in vitro, in a fashion associated with expression of B-7 co-stimulatory molecules. Thus, failure to respond to GC treatment may reflect defect in apoptosis that develop during the progressive stages of chronic inflammatory disease.
Assuntos
Apoptose/imunologia , Proteínas de Ciclo Celular , Esclerose Múltipla Crônica Progressiva/imunologia , Proteína Proteolipídica de Mielina/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Proteínas Supressoras de Tumor , Adulto , Apoptose/efeitos dos fármacos , Autoantígenos/imunologia , Células Clonais , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Ciclinas/genética , Dexametasona/farmacologia , Feminino , Expressão Gênica/imunologia , Glucocorticoides/farmacologia , Humanos , Técnicas In Vitro , Interleucina-2/genética , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/análise , Linfócitos T/efeitos dos fármacos , Fator de Crescimento Transformador beta/imunologia , Proteína Supressora de Tumor p53/genéticaRESUMO
Sheep uterine cervices and cervical mucus were heavily infiltrated by neutrophils during labour, whereas samples of cervices obtained from non-pregnant controls had no infiltrate. The neutrophilic infiltrate of the sheep uterine cervix at term was not homogeneously distributed throughout the organ: luminal mucus contained more neutrophils than tissues which, in turn, displayed a differential distribution, the superficial subepithelial layer being more heavily infiltrated than the deeper submucous layers. A widespread collagenolysis was observed in the sheep uterine cervix at term. The homogeneous morphological aspect of degradation of collagen fibres throughout the whole cervical stroma contrasted with the above-mentioned differential distribution of neutrophils. On the basis of previous reports showing that collagenolysis follows the leukocytic invasion of human and rat cervices at term, a possible role for the neutrophilic infiltrate of the sheep uterine cervix is discussed.
