Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 2, Pages 1138-1146Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.2.1138
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Funding
- NEI NIH HHS [R01EY02986, P30EY04068] Funding Source: Medline
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CD4(+) T cells produce IFN-gamma contributing to corneal perforation in C57BL/6 (136) mice after Pseudomonas aeruginosa infection. To determine the role of NK and NKT cells. infected corneas of B6 mice were dual immunolabeled. Initially, more NKT than NK cells were detected, but as disease progressed, NK cells increased, while NKT cells decreased. Therefore, B6 mice were depleted of NK/NKT cells with anti-asialo GM1 or anti-NKI.1 Ab. Either treatment accelerated time to perforation, increased bacterial load and polymorphonuclear neutrophils, but decreased IFN-gamma and IL-12p40 mRNA expression vs controls. Next, RAG-1 knockout (-/-; no T/NKT cells), B6.TCR J alpha 281(-/-) (NKT cell deficient), alpha-galactosylceramide (alpha GalCer) (anergized NKT cells) injected and IL-12p40(-/-) vs B6 controls were tested. IFN-gamma mRNA was undetectable in RAG-1(-/-) and alpha GalCer-treated mice at 5 In and was significantly reduced vs controls at I day postinfection. It also was reduced significantly in B6.TCR J alpha 281(-/-), alpha GalCer-treated, and IL-12p40(-/-) (activated CD4(+) T cells also reduced) vs control mice at 5 days postinfection. In vitro studies tested whether endotoxin (LPS) stimulated Langerhans cells and macrophages (M phi; from B6 mice) provided signals to activate NKT cells. LPS up-regulated mRNA expression for IL-12p40, costimulatory molecules CD80 and CD86, NF-KB, and CD1d, and addition of rIFN-gamma potentiated M phi CD1d levels. Together, these data suggest that Langerhans cell/M phi recognition of microbial LPS regulates IL-12p40 (and Mid) driven IFN-gamma production by NKT cells, that IFN-gamma is required to optimally activate NK cells to produce IFN-gamma, and that depletion of both NKT/NK cells results in earlier corneal perforation.
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