97th DOG Annual Meeting 1999
P79
TOPICAL CL2MDP-LIPOSOME TREATMENT ALTERS THE IMMUNE RESPONSE IN MURINE HSV-1 KERATITIS
D. Bauer1, A. Schmitz1, N. van Rooijen2, K.-P. Steuhl1, A. Heiligenhaus1
Conjunctival macrophage depletion modulates the course of murine HSV-1 keratitis. We studied the influence of subconjunctival macrophage- depletion on the immune response following a corneal HSV-1 challenge.
Methods: BALB/c mice were subconjunctivally depleted of macrophages with CL2MDP-liposomes (CL2MDP-LIP) 7 and 2 days before corneal infection with the KOS-strain of HSV-1. Mice were followed for the clinical signs of HSV keratitis. The HSV-1 antigen-specific DTH-response and virus-neutralizing antibody titers were measured after infection. IFN-gamma and IL-2 secretion (ELISA) and mRNA production (semiquantitative RT-PCR) were tested after HSV-1 infection in the infected corneas, and in lymphocytes obtained from submandibular lymph-nodes.
Results: Macrophage depletion delayed the healing of HSV-epithelial keratitis and the virus clearance from the infected eyes (day 7 p.i.: P<0.05), and improved the stromal immune process (day 14 p.i.: P<0.05). The CL2MDP-LIP-treated mice had a decreased DTH on day 14 after corneal HSV-1 infection (P<0.001) and the serum-antibody levels were increased (day 10 p.i.: P<0.05). In the mice that were macrophage depleted, the secretion of IFN-g and IL-2 was decreased both in the infected corneas and in the lymphocytes from the regional lymph-nodes after antigen-specific stimulation.
Conclusion: Macrophages appear to play various roles in HSV-1 keratitis. Beside their role in virus clearance, they may be involved in the T cell- response and in the regulation of the humoral immune response against HSV-1.
Supported by DFG grant He 1877/7-1.
1Department of Ophthalmology, University of Essen, Germany;
2Department of Cell Biology & Immunology, Vrije Universiteit, Amsterdam, The Netherlands.
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