Quantitative studies of the inflammatory process in fatal viral meningoencephalitis.

The pathogenesis of acute meningoencephalitis induced in adult mice by intravenous inoculation with Semliki Forest virus has been assessed by counting cells in cerebrospinal fluid (CSF). Meningitis was first apparent on day 4 and, by the time that animals were moribund 2 days later, each microliter of CSF contained in excess of 10,000 mononuclear cells. The following conclusions were made concerning this very considerable inflammatory response: a) Complete suppression of cellular infiltration makes no difference to the clinical disease. b) No correlation is apparent between inflammation and levels of circulating antibody. c) Participation of thymus-derived lymphocytes (T cells) is essential for full expression, though not for initiation, of cellular invasion. d) There is evidently no requirement for lymphocytes recently derived from thymus or for any humoral factor secreted by thymus tissue. e) T cells entering the recirculating pool more than 6 weeks or less than about 1 week prior to inoculation of virus are equally effective in promoting inflammation. f) The T cells apparently act directly by enhancing infiltration of other blood-borne mononuclears into the brain and CSF.