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 cells and in T-cell development. IL-2 is also implicated in autoimmune disease, although its role is still controversial. 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 mouse. Among SLE mice, the MRL/lpr strain develops early in life autoimmune diseases such as immune complex-mediated glomerulonephritis, arthritis and arteritis. 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 mice using live vaccinia recombinant viruses expressing the human IL-2 gene. 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.
Gutierrez-Ramos
J C
JC
Centro de Biologia Molecular del CSIC, Universidad Autonoma de Madrid, Spain.
Andreu
J L
JL
Revilla
Y
Y
Viñuela
E
E
Martinez
C
C
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015551:Autoimmunity; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D003176:Complement C3 / Q000032:analysis; D004274:DNA, Recombinant; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D014162:Transfection; D014616:Vaccinia virus
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003176:Complement C3; D004274:DNA, Recombinant; D007074:Immunoglobulin G; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell