Treatment with IL2/vaccinia recombinant virus leads to serologic, histologic and phenotypic normalization of autoimmune MRL/lpr-lpr mice.
We have analyzed the effect of IL2 administered in vivo on both the lymphoproliferation and autoimmune disease progression of MRL/lpr mice. Human IL2 was delivered by infecting MRL/lpr mice with vaccinia virus recombinants at different stages of lpr disease. The results reported here showed that treatment of lpr mice with IL2 mediated: (1) restored normal thymic differentiation illustrated by an expansion of the double positive population accompanied by increased numbers of mature thymocytes; (2) depletion of the peripheral CD3+ CD4- CD8- (DN) T-cell population; (3) normalization in the pattern of TcRV beta gene expression displayed by mature T cells; (4) decreased urine-protein levels and immune complex deposition in the kidney, with a resultant absence of glomerulonephritis; and (5) an increased longevity (from 195 to more than 400 days). We speculate that the dramatic reduction in the abnormally expanded CD3+ DN T-cell population following IL2 therapy might be directly related to the amelioration and/or prevention of autoimmune disease in these mice. Collectively, these results suggest that diseases showing a selective expansion of DN cells should be envisaged as possible targets for the treatment described here.
Gutierrez-Ramos
J C
JC
Centro de Biologia Molecular (CSIC-UAM), Universidad Autonoma de Madrid, Spain.
Andreu
J L
JL
Marcos
M A
MA
Vegazo
I R
IR
Martinez
C
C
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D011995:Recombination, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D007376:Interleukin-2