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Differential CD28 and inducible costimulatory molecule signaling requirements for protective CD4+ T-cell-mediated immunity against genital tract Chlamydia trachomatis infection.
Marks, Ellen; Verolin, Martina; Stensson, Anneli; Lycke, Nils.
Afiliação
  • Marks E; Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, Gothenburg University, Box 435, 40530 Gothenburg, Sweden.
Infect Immun ; 75(9): 4638-47, 2007 Sep.
Article em En | MEDLINE | ID: mdl-17635872
Th1 cells and gamma interferon (IFN-gamma) production play critical roles in protective immunity against genital tract infections by Chlamydia trachomatis. Here we show that inducible costimulatory molecule (ICOS)(-/-) mice develop greatly augmented host resistance against chlamydial infection. Protection following a primary infection was characterized by strong Th1 immunity with enhanced CD4(+) T-cell-mediated IFN-gamma production in the genital tract and high expression of T-bet in the draining para-aortic lymph node. This Th1 dominance was associated with low expression of interleukin 10 (IL-10) mRNA in the uteruses of protected ICOS(-/-) mice. By contrast, CD28(-/-) mice were severely impaired in their adaptive immune response, demonstrating a lack of CD4(+) T cells and IFN-gamma in the genital tract, with a substantial delay in bacterial elimination compared to that seen in wild-type (WT) mice. Upon reinfection, WT mice exhibited a transient local infection with evidence of regulatory T-cell (Treg)/Foxp3 mRNA and a more balanced Th1 and Th2 response in the genital tract than ICOS(-/-) mice, whereas 90% of the latter mice developed sterile immunity, poor expression of local Treg/Foxp3 mRNA, and macroscopic signs of enhanced local immunopathology. Therefore, different requirements for CD28 signaling and ICOS signaling clearly apply to host protection against a genital tract infection by C. trachomatis. Whereas, CD28 signaling is critical, ICOS appears to be dispensable and can have a dampening effect on Th1 development by driving Th2 immunity and anti-inflammation through IL-10 production and promotion of the Foxp3(+) Treg populations in the genital tract. Both the CD28-deficient and the ICOS-deficient mice demonstrated poor specific antibody production, supporting the fact that antibodies are not needed for protection against genital tract chlamydial infections.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Transdução de Sinais / Infecções por Chlamydia / Antígenos de Diferenciação de Linfócitos T / Antígenos CD28 Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Transdução de Sinais / Infecções por Chlamydia / Antígenos de Diferenciação de Linfócitos T / Antígenos CD28 Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article