Anti-CD3 immunotoxin prevents low-dose STZ/interferon-induced autoimmune diabetes in mouse

Taenia crassiceps, like other helminths, can exert regulatory effects on the immune system of its host. This study investigates the effect of chronicT. crassicepsinfection on the outcome of Multiple Low Dose Streptozotocin-Induced Diabetes (MLDS). Healthy or previouslyT. crassiceps-infected mice received MLDS and type 1 diabetes (T1D) symptoms were evaluated for 6 weeks following the induction of MLDS.T. crassiceps-infected mice displayed lower blood glucose levels throughout the study. A significantly lower percentage ofT. crassiceps-infected mice (40%) developed T1D compared to the uninfected group (100%). Insulitis was remarkably absent inT. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. Infected mice that received MLDS did not show an increase in their regulatory T cell population, however, they had a greater number of alternatively activated macrophages, higher levels of the cytokine IL-4, and lower levels of TNF-α. Therefore, infection withT. crassicepscauses an immunomodulation that modifies the incidence and development of MLDS-induced autoimmune diabetes.

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Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells

International Journal of Molecular Sciences ◽

10.3390/ijms222312988 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12988

Author(s):

Zhengkang Luo ◽

Sara Lundin ◽

Mariela Mejia-Cordova ◽

Imane Hassani ◽

Martin Blixt ◽

...

Keyword(s):

B Cells ◽

Low Dose ◽

Autoimmune Diabetes ◽

Healthy Controls ◽

Regulatory B Cells ◽

Experimental Autoimmune Uveitis ◽

Ifn Γ ◽

Experimental Autoimmune

The anti-inflammatory role of regulatory B cells (Breg cells) has been associated with IL-35 based on studies of experimental autoimmune uveitis and encephalitis. The role of Breg cells and IL-35+ Breg cells for type 1 diabetes (T1D) remains to be investigated. We studied PBMCs from T1D subjects and healthy controls (HC) and found lowered proportions of Breg cells and IL-35+ Breg cells in T1D. To elucidate the role of Breg cells, the lymphoid organs of two mouse models of T1D were examined. Lower proportions of Breg cells and IL-35+ Breg cells were found in the animal models of T1D compared with control mice. In addition, the systemic administration of recombinant mouse IL-35 prevented hyperglycemia after multiple low dose streptozotocin (MLDSTZ) injections and increased the proportions of Breg cells and IL-35+ Breg cells. A higher proportion of IFN-γ+ cells among Breg cells were found in the PBMCs of the T1D subjects. In the MLDSTZ mice, IL-35 administration decreased the proportions of IFN-γ+ cells among the Breg cells. Our data illustrate that Breg cells may play an important role in the development of T1D and that IL-35 treatment prevents the development of hyperglycemia by maintaining the phenotype of the Breg cells under an experimental T1D condition.

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Effect of Modified Diabetic Splenocytes on Mice Injected with Multiple Low-Dose Streptozotocin

Experimental Biology and Medicine ◽

10.1177/153537020222700409 ◽

2002 ◽

Vol 227 (4) ◽

pp. 282-289 ◽

Cited By ~ 5

Author(s):

Claudia Pastorale ◽

Mabel Arata ◽

Andrea Caminos ◽

Lidia Bruno ◽

Juan Basabe ◽

...

Keyword(s):

Insulin Secretion ◽

Pancreatic Islets ◽

Low Dose ◽

Mononuclear Cells ◽

Islet Cells ◽

Autoimmune Diabetes ◽

Cellular Death ◽

Cell Destruction ◽

Perifused Islets ◽

Delta Cells

This work reports the effects of a previous injection of mitomycin-modified splenocytes from multiple-low dose streptozotocin-treated mice (mld-sz) on autoimmune diabetes produced by mld-sz. Our work shows that a previous inoculation of modified mononuclear splenocytes from mld-sz mice prevents alterations in glycemia, in insulin secretion (IS) pattern from isolated perifused islets, and in mass of pancreatic islets. Immunohistochemistry showed an alteration in the number of beta, but not of alpha or delta cells. While a mononuclear intra-islet infiltration was observed in mld-sz mice, a predominantly polar or peri-islet infiltration was seen in vaccinated mice. Islet-associated mononuclear cells from mld-sz mice produced diabetes and induced a diminished IS when transferred to normal receptors. Those cells from previously vaccinated mld-sz mice had no effect when injected into normal receptors. In addition, they also inhibited the damage induced in normal receptors by the islet-associated mononuclear cells from mld-sz animals. Cellular death was also prevented by previous vaccination. Our results suggest that vaccination with modified splenocytes from mld-sz mice is capable of shifting the islet cells infiltration pattern from an aggressive one toward a protective one and thus preventing the ß cell destruction observed in mld-sz mice.

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