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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.

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Related in: MedlinePlus

Anemia in the IL-4 tg mice. (A) Survival rate of IL-4 tg  mice. IL-4 tg (n = 31) and littermate control mice (n = 20) were monitored daily for 12 wk  and the death of mice recorded. Shown is the survival rate of the mice in percentage. (B and C) Hematocrit counts and percentage of reticulocyte numbers in the blood of 4- and 12-wk-old IL-4 tg  and control mice.
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Figure 1: Anemia in the IL-4 tg mice. (A) Survival rate of IL-4 tg mice. IL-4 tg (n = 31) and littermate control mice (n = 20) were monitored daily for 12 wk and the death of mice recorded. Shown is the survival rate of the mice in percentage. (B and C) Hematocrit counts and percentage of reticulocyte numbers in the blood of 4- and 12-wk-old IL-4 tg and control mice.

Mentions: IL-4 tg mice of this particular line have a very high mortality rate (Fig. 1 A) and suffer from severe anemia as seen by the dramatic decrease in hematocrit (Fig. 1 B) and increase in reticulocyte numbers in the blood (Fig. 1 C). Furthermore, IL-4 tg mice showed extramedullary hematopoiesis in spleen and liver with elevated bilirubin levels in the blood (data not shown). These observations suggested that the mice develop an autoantibody-induced hemolytic anemia (AIHA). Staining of blood smears with rabbit anti–mouse Ig revealed that some of the tg mice with the most severe anemia had detectable levels of antibodies bound to their erythrocytes. However, a coombs test using erythrocytes from IL-4 tg mice and goat or rabbit anti–mouse total Ig failed to detect autoantibodies binding to the erythrocytes from the IL-4 tg mice (data not shown).


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)

Anemia in the IL-4 tg mice. (A) Survival rate of IL-4 tg  mice. IL-4 tg (n = 31) and littermate control mice (n = 20) were monitored daily for 12 wk  and the death of mice recorded. Shown is the survival rate of the mice in percentage. (B and C) Hematocrit counts and percentage of reticulocyte numbers in the blood of 4- and 12-wk-old IL-4 tg  and control mice.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Anemia in the IL-4 tg mice. (A) Survival rate of IL-4 tg mice. IL-4 tg (n = 31) and littermate control mice (n = 20) were monitored daily for 12 wk and the death of mice recorded. Shown is the survival rate of the mice in percentage. (B and C) Hematocrit counts and percentage of reticulocyte numbers in the blood of 4- and 12-wk-old IL-4 tg and control mice.
Mentions: IL-4 tg mice of this particular line have a very high mortality rate (Fig. 1 A) and suffer from severe anemia as seen by the dramatic decrease in hematocrit (Fig. 1 B) and increase in reticulocyte numbers in the blood (Fig. 1 C). Furthermore, IL-4 tg mice showed extramedullary hematopoiesis in spleen and liver with elevated bilirubin levels in the blood (data not shown). These observations suggested that the mice develop an autoantibody-induced hemolytic anemia (AIHA). Staining of blood smears with rabbit anti–mouse Ig revealed that some of the tg mice with the most severe anemia had detectable levels of antibodies bound to their erythrocytes. However, a coombs test using erythrocytes from IL-4 tg mice and goat or rabbit anti–mouse total Ig failed to detect autoantibodies binding to the erythrocytes from the IL-4 tg mice (data not shown).

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