Diabetogenic T cells induce autoimmune diabetes in BALB/c mice.
OBJECTIVE
To investigate the role of T cell and its subsets in the induction of insulitis and type 1 diabetes mellitus (T1DM) in BALB/c mice.


METHODS
Autoimmune diabetes mellitus was developed by intraperitoneal injection of 40 mg/kg streptozotocin (STZ) daily for 5 consecutive days in BALB/c mice as sources of donor cells. Spleen cells from diabetic mice were then cultured for 7 days in the stimulation of interleukin-2 (IL-2) to harvest diabetogenic T cells, which were subsequently transferred into normal BALB/c mice recipients. MTT, ELISA, and HE staining were used to analyze the lymphocyte proliferation, cytokine (IL-2, interferon-gamma, IL-4, and IL-10) levels, and pathological changes in pancreatic islets.


RESULTS
As few as 3 x 10(6) diabetogenic T cells successfully induced diabetes mellitus in recipients pretreated with STZ twice, whereas transfer of equal amount of normal splenocytes, T cell-depleted diabetogenic splenocytes, or diabetogenic CD4+ T cells alone in recipients receiving STZ twice pretreatment was proved not to induce diabetes mellitus either. A markedly increased lymphocyte proliferation, high levels of interferon-gamma and IL-2 in the supernatants of diabetogenic T cells were observed. In addition, a markedly enhanced lymphocyte proliferation, a high level of interferon-gamma secretion in serum, and numerous lymphocytes infiltration in pancreatic islets were detected in the diabetic mice induced by diabetogenic T cells transfer.


CONCLUSIONS
A novel T1DM murine model is established in STZ-pretreated BALB/c mice by adoptive transfer of diabetogenic T cells. CD4+ T cells with interferon-gamma may promote the onset of diabetes mellitus.
Zou
Xiao-Lei
XL
Department of Pharmacology, College of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.
Zhao
Zeng-Yu
ZY
Wang
Yun-Yang
YY
Su
Zhi-Qiang
ZQ
Xiang
Ming
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D001786:Blood Glucose; D016207:Cytokines