RESUMO
Chronic granulomatous disease (CGD) patients are highly susceptible to invasive aspergillosis and might benefit from aspergillus-specific T cell immunotherapy, which has shown promise in treating those with known T cell defects such as haematopoietic stem cell transplant (HSCT) recipients. But whether such T cell defects contribute to increased risks for aspergillus infection in CGD is unclear. Hence, we set out to characterize the aspergillus-specific T cell response in CGD. In murine CGD models and in patients with CGD we showed that the CD4(+) T cell responses to aspergillus were unimpaired: aspergillus-specific T cell frequencies were even elevated in CGD mice (P < 0·01) and humans (P = 0·02), compared to their healthy counterparts. CD4-depleted murine models suggested that the role of T cells might be redundant because resistance to aspergillus infection was conserved in CD4(+) T cell-depleted mice, similar to wild-type animals. In contrast, mice depleted of neutrophils alone or neutrophils and CD4(+) T cells developed clinical and pathological evidence of pulmonary aspergillosis and increased mortality (P < 0·05 compared to non-depleted animals). Our findings that T cells in CGD have a robust aspergillus CD4(+) T cell response suggest that CD4(+) T cell-based immunotherapy for this disease is unlikely to be beneficial.
Assuntos
Aspergilose Broncopulmonar Alérgica/imunologia , Aspergilose Broncopulmonar Alérgica/terapia , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/terapia , Imunoterapia Adotiva , Linfócitos T/imunologia , Linfócitos T/microbiologia , Animais , Aspergillus fumigatus/imunologia , Linhagem Celular , Células Cultivadas , Humanos , Imunoterapia Adotiva/métodos , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 2 , NADPH Oxidases/deficiência , NADPH Oxidases/genética , Linfócitos T/patologia , Células Th1/imunologia , Células Th1/microbiologia , Células Th1/transplanteRESUMO
An appliance is described for the rehabilitation of patients following hemimandibulectomy. It has the advantages, over traditional prostheses, of being quick, simple and cheap to produce.