IMMUNOPATHOGENIC ROLE OF T-CELL SUBSETS IN BORNA-DISEASE VIRUS-INDUCED PROGRESSIVE ENCEPHALITIS

Borna disease is an immunopathological virus-induced encephalopathy co mprising severe inflammation and degenerative brain cell lesions which results in organ atrophy and chronic debility in rats, CD4(+) and CD8 (+) T-cells have been reported to be involved in the development of th is disease of the central nervous system, A virus-specific homogeneous T-cell line, established in vitro after immunization of rats with the recombinant 24-kDa virus-specific protein, showed antigen-specific pr oliferation in the presence of the 24-kDa but not the 38-kDa Borna dis ease virus-specific protein, another major virus-specific antigen, Thi s T-cell line, P205, was found to exhibit characteristics of a T-helpe r cell: CD4(+) CD8(-) IL-2(-) IL-4(-) IFN-gamma(+) IL-6(+) IL-10(+). F urthermore, this T-cell line expressed the alpha/beta T cell receptor and the alpha 4 integrin (VLA-4), Adoptive transfer of this helper cel l resulted in an increase of antibody titers and two different types o f disease in virus-infected rats after cyclophosphamide induced immuno suppression, (i) Rats receiving T-cells between 10 and 18 days after t reatment with cyclophosphamide showed an acute lymphoproliferative dis ease in the gut and lungs within 9 days after adoptive transfer and di ed, (ii) Passive transfer within the first 5 days after immunosuppress ive treatment resulted in typical Borna disease associated with neurol ogical symptoms such as ataxia and paresis starting 14 to 16 days afte r transfer, Immunohistological analysis of the brains of rats with Bor na disease uniformly revealed the presence of CD8(+) T-cells in enceph alitic lesions in addition to CD4(+) cells that were found in the brai ns of recipients of the virus-specific CD4(+) T-cell line, irrespectiv e of whether neurological symptoms developed or not, However, recipien t rats treated with antibodies against CD8(+) T-cells developed neithe r encephalitis nor disease, Therefore, CD4(+) T cells appear to accumu late in the brain and cause perivascular inflammatory lesions which al one obviously do not cause disease. In contrast, the presence of CD8() cells apparently directly correlates with the development of neurolo gical symptoms,