Limits...
Constitutive expression of interleukin (IL)-4 in vivo causes autoimmune-type disorders in mice.

Erb KJ, Rüger B, von Brevern M, Ryffel B, Schimpl A, Rivett K - J. Exp. Med. (1997)

Bottom Line: The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels.Therefore the most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner.Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.

View Article: PubMed Central - PubMed

Affiliation: The Malaghan Institute of Medical Research, Department of Medicine, Wellington School of Medicine, New Zealand.

ABSTRACT
The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels. Tg mice develop anemia, glomerulonephritis with complement and immune deposition in the glomeruli, and show increased production of autoantibodies. Treatment of IL-4 tg mice with anti-IL-4 neutralizing antibodies protected the mice from disease development, showing that IL-4 was responsible for the observed disorders. Deletion of superantigen responsive autoreactive T cells in the IL-4 tg mice was normal and treatment of mutant mice with deleting anti-CD4 antibodies failed to ablate the onset of autoimmune-like disease, suggesting that CD4+ T cells were not the primary cause of the disorders. Furthermore, the deletion of B cells reacting against MHC class I molecules was also normal in the IL-4 tg mice. Therefore the most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner. Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.

Show MeSH

Related in: MedlinePlus

Immune deposits in  the kidneys of IL-4 tg mice. The  kidneys of an IL-4 tg (A) and  control mouse (B) were fixed in  formalin and stained with peroxidase conjugated rabbit anti–mouse  total Ig. Ig binding was visualized through the addition of diaminobenzidine. Shown is a representative example of immune  deposition detected in IL-4 tg  mice (n = 20). g, glomerulus.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196114&req=5

Figure 2: Immune deposits in the kidneys of IL-4 tg mice. The kidneys of an IL-4 tg (A) and control mouse (B) were fixed in formalin and stained with peroxidase conjugated rabbit anti–mouse total Ig. Ig binding was visualized through the addition of diaminobenzidine. Shown is a representative example of immune deposition detected in IL-4 tg mice (n = 20). g, glomerulus.

Mentions: Kidneys of IL-4 tg mice showed progressive glomerular damage with complement and Ig deposition in glomeruli (Fig. 2) and developed progressive glomerular hypertrophy and glomerulosclerosis. The antibodies present in the kidneys of IL-4 tg mice were of the IgM, IgG1, IgG2a, and IgA but not IgE isotypes (data not shown). On electron microscopy the deposits were predominantly localized to subendothelial and mesangial areas (data not shown). Most, but not all, of the glomeruli in the kidneys of IL-4 tg mice showed signs of damage. IL-4 tg mice showing signs of wasting syndrome (n = 6) had an average 10-fold decrease in urine volume (measured over 24-h period) and a 6-fold increase in urinary protein excretion as compared to littermate control mice (Rüger, B., unpublished observation).


Constitutive expression of interleukin (IL)-4 in vivo causes autoimmune-type disorders in mice.

Erb KJ, Rüger B, von Brevern M, Ryffel B, Schimpl A, Rivett K - J. Exp. Med. (1997)

Immune deposits in  the kidneys of IL-4 tg mice. The  kidneys of an IL-4 tg (A) and  control mouse (B) were fixed in  formalin and stained with peroxidase conjugated rabbit anti–mouse  total Ig. Ig binding was visualized through the addition of diaminobenzidine. Shown is a representative example of immune  deposition detected in IL-4 tg  mice (n = 20). g, glomerulus.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196114&req=5

Figure 2: Immune deposits in the kidneys of IL-4 tg mice. The kidneys of an IL-4 tg (A) and control mouse (B) were fixed in formalin and stained with peroxidase conjugated rabbit anti–mouse total Ig. Ig binding was visualized through the addition of diaminobenzidine. Shown is a representative example of immune deposition detected in IL-4 tg mice (n = 20). g, glomerulus.
Mentions: Kidneys of IL-4 tg mice showed progressive glomerular damage with complement and Ig deposition in glomeruli (Fig. 2) and developed progressive glomerular hypertrophy and glomerulosclerosis. The antibodies present in the kidneys of IL-4 tg mice were of the IgM, IgG1, IgG2a, and IgA but not IgE isotypes (data not shown). On electron microscopy the deposits were predominantly localized to subendothelial and mesangial areas (data not shown). Most, but not all, of the glomeruli in the kidneys of IL-4 tg mice showed signs of damage. IL-4 tg mice showing signs of wasting syndrome (n = 6) had an average 10-fold decrease in urine volume (measured over 24-h period) and a 6-fold increase in urinary protein excretion as compared to littermate control mice (Rüger, B., unpublished observation).

Bottom Line: The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels.Therefore the most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner.Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.

View Article: PubMed Central - PubMed

Affiliation: The Malaghan Institute of Medical Research, Department of Medicine, Wellington School of Medicine, New Zealand.

ABSTRACT
The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels. Tg mice develop anemia, glomerulonephritis with complement and immune deposition in the glomeruli, and show increased production of autoantibodies. Treatment of IL-4 tg mice with anti-IL-4 neutralizing antibodies protected the mice from disease development, showing that IL-4 was responsible for the observed disorders. Deletion of superantigen responsive autoreactive T cells in the IL-4 tg mice was normal and treatment of mutant mice with deleting anti-CD4 antibodies failed to ablate the onset of autoimmune-like disease, suggesting that CD4+ T cells were not the primary cause of the disorders. Furthermore, the deletion of B cells reacting against MHC class I molecules was also normal in the IL-4 tg mice. Therefore the most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner. Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.

Show MeSH
Related in: MedlinePlus