RECOVERY FROM AUTOIMMUNITY OF MRL LPR MICE AFTER INFECTION WITH AN INTERLEUKIN-2 VACCINIA RECOMBINANT VIRUS

INTERLEUKIN-2 (IL-2) is a T-cell derived molecule implicated in the clonal expansion of antigen-activated T cells1 and in T-cell development2. IL-2 is also implicated in autoimmune disease3, although its role is still controversial4,5. Murine systemic lupus erythematosus (SLE) is a good model for human SLE as most of the immunological abnormalities in the human disease also seem to be operative in the mouse6. Among SLE mice, the MRL/lpr strain develops early in life autoimmune diseases such as immune complex-mediated glomerulonephritis, arthritis and arteritis7,8. Lymphoid abnormalities associated with those diseases in this strain are thymic atrophy and abnormal proliferation of CD3+ CD4- CD8- 'double-negative' T cells, resulting in massive generalized lymph node enlargement. We have therefore now examined the effects of IL-2 on the disease progression in MRL/lpr mice9 using live vaccinia recombinant viruses expressing the human IL-2 gene10. Vaccinated mice showed prolonged survival, decreased autoantibody and rheumatoid factor titres, marked attenuation of kidney interstitial infiltration and intraglomerular proliferation, as well as clearance of synovial mononuclear infiltrates. Inoculation with the IL-2/vaccinia recombinant virus led, in addition, to drastic reduction of the double-negative T-cell population, improved thymic differentiation and restoration of normal values of mature cells in peripheral lymphoid organs. © 1990 Nature Publishing Group.