Rabies virus ocular disease: T-cell-dependent protection is under the control of signaling by the p55 tumor necrosis factor alpha receptor, p55TNFR

Following brain infection, the Challenge Virus Standard strain of rabies vi rus infects the retina. Rabies virus ocular infection induces the infiltrat ion of neutrophils and predominantly T cells into the eye. The role of tumo r necrosis factor alpha (TNF-alpha)-lymphotoxin signaling in the control of rabies virus ocular infection and inflammatory cell infiltration was asses sed using mire lacking the p55 TNF-alpha receptor (p55TNFR(-/-) mice). The incidence of ocular disease and the intensity of retinal infection were gre ater in p55TNFR(-/-) mice than in C57BL/6 mice: the aggravation correlated with less neutrophil and T-cell infiltration. This indicates that cellular infiltration is under the control of the p55 TNF-alpha receptor and suggest s that inflammatory cells may protect the eye against rabies virus ocular i nfection. The role of T cells following rabies virus ocular disease was ass essed by comparison of rabies virus infection in nude mice with their norma l counterparts. Indeed, the incidence and severity of the rabies virus ocul ar disease were higher in athymic nude mice than in BALB/c mice, indicating that T lymphocytes are protective during rabies virus ocular infection. Mo reover, few T cells and neutrophils underwent apoptosis in rabies virus-inf ected retina. Altogether, these data suggest that T lymphocytes and neutrop hils are able to enter the eye, escape the immune privilege status, and lim it rabies virus ocular disease. In conclusion, rabies virus-mediated eye di sease provides a new model for studying mechanisms regulating immune privil ege during viral infection.