Dominance of CD86, transforming growth factor- beta 1, and interleukin-10 in Mycobacterium tuberculosis secretory antigen-activated dendritic cells regulates T helper 1 responses to mycobacterial antigens.
J Infect Dis
; 189(9): 1598-609, 2004 May 01.
Article
em En
| MEDLINE
| ID: mdl-15116295
ABSTRACT
We report that stimulation of Mycobacterium tuberculosis (M. tuberculosis) secretory antigen (MTSA)-differentiated dendritic cells (DCs) and MTSA-matured DCs with M. tuberculosis cell extract (CE) down-regulated proinflammatory responses to CE-primed T (CE-T) cells by increasing surface expression of CD86 after CE stimulation. CE stimulation also decreased interleukin (IL)-12p40 and interferon (IFN)- gamma levels and increased IL-10 and transforming growth factor- beta 1 (TGF- beta 1) levels from these DCs. Blocking either CD86, IL-10, or TGF- beta with monoclonal antibodies before CE stimulation restored the attenuated T helper 1 (Th1) responses of CE-T cells. Conversely, treatment of these DCs with IL-12p70 and/or IFN- gamma completely restored Th1 responses from CE-T cells. These results indicate that M. tuberculosis secretory antigens down-regulate proinflammatory Th1 responses to mycobacteria by differentially modulating the cytokine profiles and surface densities of costimulatory molecules on DCs. Of importance, this down-regulation is independent of the maturation status of MTSA-activated DCs and can be rescued after treatment of DCs with IFN- gamma or IL-12.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Glicoproteínas de Membrana
/
Antígenos CD
/
Regulação para Baixo
/
Fator de Crescimento Transformador beta
/
Interleucina-10
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Células Th1
/
Mycobacterium tuberculosis
Limite:
Animals
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2004
Tipo de documento:
Article