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L.D. Hazlett, Q. Li; The Role of NK and NKT Cells in P. aeruginosa Keratitis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1080.
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Previous work in this laboratory has demonstrated that after Pseudomonas aeruginosa corneal infection, unchecked production of IFN–γ by CD4+ T cells contributes to increased disease severity and corneal perforation in C57BL/6 (B6) mice. NK and a subset of T cells, NKT cells, also are sources of IFN–γ and NK cells, regulated by IL–18 and the neuropeptide Substance P, have been shown of importance in the resistance response of BALB/c mice to bacterial infection. Therefore, the purpose of the current study was to test the role of NK and NKT cells in P. aeruginosa keratitis in B6 mice.
B6 mice were depleted of NK cells using anti–asialo GM1 antibody (Ab) and both NK and NKT cells using anti–NK1.1 Ab. Finally we blocked NKT cell glycolipid presentation through CD1d using an anti–CD1d mAb (1B1). The response to disease was then monitored by immunocytochemistry, clinical score, slit lamp, plate count, myeloperoxidase activity (PMN), and real time PCR.
In about 1–5 hours after infection NKT (earlier) and NK (later) cells were detected in the cornea by dual–labeling. NK cells increased in the cornea over time, while NKT cell numbers decreased. Depletion of NK cells with either Ab accelerated corneal perforation after challenge and led to an increase in corneal bacterial load and PMN number. NK depletion also led to decreased levels of IFN–γ and IL–12 mRNA, while IL–18 and TNF–α levels were not significantly affected. Use of CD1d mAb to block glycolipid presentation in NKT cells did not change clinical score, or mRNA levels for IFN–γ or IL–12 over controls.
This study provides evidence to suggest that in B6 mice, NK cells are initially protective, but that their persistence in the cornea leads to increased IFN–γ levels and perforation. NKT cells do not appear involved in disease outcome, but have not yet been stringently tested for their possible early regulatory effects on NK cells.
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