Summary
A single dose of cyclophosphamide (250 mg/kg) is known to synchronize and accelerate development of diabetes in non-obese diabetic mice. We have reported previously that cyclophosphamide treatment of 10-week-old female non-obese diabetic mice induces a shift from T-helper type 2 to T-helper type 1 activity in islet lesions. We now show that this shift in regulatory T-cell function is preceded by the expression of interleukin-12 in the islets as well as in the spleen. In the spleen macrophages were identified as the interleukin-12 expressing cell type. At the same time there was little induction of tumour necrosis factor alpha gene expression by macrophages. Since interleukin-12 is well known to drive T-helper cell type 1 responses we assume that interleukin-12 released by macrophages mediates the accelerating effect of cyclophosphamide on islet inflammation in non-obese diabetic mice. mRNA expression of the p40 chain of interleukin-12 in response to cyclophosphamide was not seen in macrophages of Balb/c mice and thus represents an immune abnormality of non-obese diabetic mice favouring T-helper type 1 reactions.
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Abbreviations
- CY:
-
Cyclophosphamide
- FCS:
-
fetal calf serum
- G3PDH:
-
glyceraldehyde 3-phosphate dehydrogenase
- IFN-γ:
-
interferon-gamma
- IL-4:
-
interleukin-4
- IL-12:
-
interleukin-12
- NK cells:
-
natural killer cells
- NOD:
-
non-obese diabetic
- PSL:
-
phosphor stimulated luminescence
- RT-PCR:
-
reverse transcriptase polymerase chain reaction
- Th1/2:
-
T-helper cell type 1/2
- TNFα:
-
tumour necrosis factor alpha
References
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Rothe, H., Burkart, V., Faust, A. et al. Interleukin-12 gene expression is associated with rapid development of diabetes mellitus in non-obese diabetic mice. Diabetologia 39, 119–122 (1996). https://doi.org/10.1007/BF00400422
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DOI: https://doi.org/10.1007/BF00400422