T-CELL SUBSETS AND T-CELL RECEPTOR V-BETA UTILIZATION BY IGH-1-CONGENIC MICE IN HERPETIC RETINAL NECROSIS

Background: After unilateral anterior chamber (AC) inoculation with he rpes simplex virus type 1 (HSV-1), C.B-17 and BALB/c congenic mice, wh ich differ only in a limited region around the Igh-1 locus on chromoso me 12, show a striking difference in susceptibility to development of encephalitis and contralateral necrotizing chorioretinitis. Methods: A fter AC inoculation with HSV-1 (KOS), C.B-17 and BALB/c mice were foll owed up for the clinical signs of encephalitis and chorioretinitis. At different time points following inoculation, lymphocytes isolated fro m the spleen were triple-stained with antibodies directed against CD4 or CD8, IL-2R, and various V beta T-cell receptor (TCR) subsets, and w ere analyzed by flow cytometry. Results: These Igh-1-disparate congeni c mice showed differences in the time course of splenic V beta T-cell receptor (TCR) usage in both CD4+, IL-2R+ and CD8+, IL-2R+ T cells. By day 1 post infection (p.i.), C.B-17 mice showed an increase of V beta 8 and V beta 9 TCR by both CD4+, IL-2R+ and CD8+, IL-2R+ splenic T ce lls. Susceptible BALB/c mice delayed the increase of splenic V beta 8 and V beta 9 TCR by CD4+, IL-2R+ T cells, which was noted by day 4 p.i . Furthermore, in BALB/c mice the usage of V beta 9 by CD8+ cells was increased by day 6 p.i. Conclusions: Our findings indicate that early preferential splenic usage of a restricted repertoire of TCR occurs af ter ocular inoculation with HSV-1 in resistant C.B-17 mice. Such prefe rential TCR usage by activated T cells may prevent viral replication i n the brain and contralateral eye and may be linked to protection from development of encephalitis and destructive herpes-mediated ocular in flammation.