IMMUNE-RESPONSES LIMIT ADENOVIRALLY MEDIATED GENE-EXPRESSION IN THE ADULT-MOUSE EYE

In order to investigate the immunological consequences of gene transfe r to the eye using viral vectors, adenovirus carrying a lacZ reporter gene (AV.LacZ) was injected either subretinally, subconjunctivally or into the anterior chamber of three groups of adult mice: immunocompete nt or transiently immunosuppressed BALB/c mice and congenic immunodefi cient nude mice. Adenovirally mediated lacZ expression persisted for a pproximately 3 weeks following injection of the vector into the anteri or chamber, retina or extra ocular tissues of the conjuctiva of BALB/c mice. It appears that T cell-mediated immune responses limit the dura tion of AV-mediated ocular gene expression in adult mice since lacZ ge ne expression was detected for at least 15 weeks in T cell-deficient B ALB/c nude mice, although the level of transgene expression decreased with time. Since intra-ocular AV-mediated gene expression was not sign ificantly longer than extra-ocular expression, it appears that the eye is not normally immune-privileged with respect to viral vectors. Infl ammatory cells were detected in the vitreous after anterior chamber in jection and in the retina after subretinal injection of adenovirus. Th e presence of both CD4(+) and CD8(+) T cells was established by immuno phenotyping. Reinjection of BALB/c mice resulted in rapid decline in r eporter gene expression, but successful readministration was possible in the case of immunodeficient nude mice. However, after transient dep letion of T cells, achieved by intraperitoneal injection of both CD8- and CD4-specific antibodies the duration of expression in BALB/c mice was longer in the eye (at least 12 weeks, again with decrease in level over time), than in extra-ocular tissues (8 weeks) provided the anima l was not reinjected with virus, raising the possibility of partial oc ular immune-privilege after transient immunosuppression.