Assuntos
Endotélio Vascular/patologia , Malária Cerebral/sangue , Fatores de Coagulação Sanguínea/genética , Moléculas de Adesão Celular/genética , Endotélio Vascular/química , Humanos , Prognóstico , RNA Mensageiro/sangue , Receptores de Superfície Celular/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
To characterize the T cells involved in the pathogenesis of cerebral malaria (CM) induced by infection with Plasmodium berghei ANKA clone 1.49L (PbA 1.49L), the occurrence of the disease was assessed in mice lacking T cells of either the alphabeta or gammadelta lineage (TCRalphabeta(-/-) or TCRgammadelta(-/-)). TCRgammadelta(-/-) mice were susceptible to CM, whereas all TCRalphabeta(-/-) mice were resistant, suggesting that T cells of the alphabeta lineage are important in the genesis of CM. The repertoire of TCR V(beta) segment gene expression was examined by flow cytometry in B10.D2 mice, a strain highly susceptible to CM induced by infection with PbA 1.49L. In these mice, CM was associated with an increase of T cells bearing the V(beta)8.1, 2 segments in the peripheral blood lymphocytes. Most V(beta)8.1, 2(+) T cells from peripheral blood lymphocytes of the mice that developed CM belonged to the CD8 subset, and exhibited the CD69(+), CD44(high) and CD62L(low) phenotype surface markers. The link between the increase in V(beta)8.1, 2(+) T cells and the neuropathological consequences of PbA infection was strengthened by the observation that the occurrence of CM was significantly reduced in mice treated with KJ16 antibodies against the V(beta)8.1 and V(beta)8.2 chains, and in mice rendered deficient in V(beta)8.1(+) T cells by a mouse mammary tumor virus superantigen.
Assuntos
Malária Cerebral/imunologia , Plasmodium berghei , Receptores de Antígenos de Linfócitos T/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Antígenos CD4/genética , Genes Codificadores dos Receptores de Linfócitos T/genética , Contagem de Linfócitos , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
Infection with Plasmodium berghei ANKA is usually lethal. The parasite causes in some mouse strains a neurovascular syndrome, experimental cerebral malaria (ECM), involving immunopathological reactions. The effects on the development of ECM of the mouse genetic background have been clearly demonstrated, but nothing is known about the effects of the clonal diversity of the parasite. We showed that various cloned lines derived from a polyclonal line of P. berghei ANKA caused ECM but that the extent of ECM induction was dependent on the amount of inoculum. Subtle differences in ECM characteristics (survival time and hypothermia) were also observed. We also confirmed, using the 1.49L cloned line, that the mouse genetic background strongly affects ECM.
