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S.J. Molesworth–Kenyon, J.E. Oakes, R. Lausch; Abundant Expression of IP–10 and Mig in the HSV–1 Infected Cornea. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):120.
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Purpose: CD4+ T lymphocytes are important responding effector cells following HSV–1 corneal infection. However, the chemokines responsible for recruiting these cells have not yet been clearly defined. Since activated CD4+ T cells express CXCR3 we tested whether IP–10 and Mig, ligands for this receptor, are produced following primary and secondary corneal infection. Methods: C57Bl/6 mice were infected topically on the scarified cornea with HSV–1 strain RE. Hosts were sensitized by giving the virus in the footpads and ear pinnas 10 days prior to ocular challenge. Chemokine messenger RNA levels were assessed via real time PCR and protein levels were quantified by ELISA. Neutrophil depletion was achieved by intraperitoneal injection of 1 mg mAb RB6 8C5 given 6 hrs prior to virus infection. Results: Our initial studies established that low levels of IP–10 were made constitutively in the murine cornea while Mig was not detectable. Forty–eight hours after HSV–1 infection mRNA for both chemokines was sharply elevated (> 100 fold) in both naïve and immunized hosts. Protein kinetic studies showed that peak levels of IP–10 (862±136 pg/ml) occurred 48 h after primary infection. In the same timeframe Mig levels were some 4–fold lower. However, while Mig levels remained high at days 6–8 p.i. IP–10 returned to constitutive levels. In contrast to naïve hosts Mig levels in immunized mice at 48 h p.i. were >2–fold higher than IP–10. We tested whether resident corneal cells produce IP–10 and Mig. When normal corneas were excised and incubated ex vivo for 10–24 h substantial levels (>100 pg/ml) of IP–10 were detected in the culture supernatants whereas no Mig was seen. In addition neutrophils purified from bone marrow and stimulated with IFN–γ produce substantial levels of IP–10 (>1500 pg/ml) and Mig (>500 pg/ml). Conclusions:Both IP–10 and Mig are generated in abundance in the cornea after HSV–1 infection. IP–10 protein is detectable more than 24 h earlier than Mig and its cellular sources include both resident corneal cells and neutrophils. Infiltrating leukocytes including neutrophils may be the principal cellular sources of Mig.
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