Responses of Canine Lymphocytes to Allogeneic and Autologous Islets of Langerhans in Mixed Cell Cultures

Rabinovitch, Alex; Fuller, Laphalle; Mintz, Daniel H.; Severyn, Walter; Noel, Jack; Flaa, Cathy; Kyriakides, George; Miller, Joshua D.

doi:10.1172/jci110181

Cited by 14 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our observations are in accordance with recent studies of primary and secondary lymphoproliferative responses with islet cells and lymphocytes from dogs (Rabinovitch et al 1981). The authors of those studies observed a primary proliferative response to islet cells.…”

Section: Discussionsupporting

confidence: 94%

In vitro lymphocyte recognition of islet cells following in vivo priming with allogeneic murine pancreatic islets

Scott¹,

MacKay²,

Lernmark³

1984

Acta Endocrinologica

View full text Add to dashboard Cite

Lymphocytes from patients with i nsul i n\x=req-\ dependent diabetes have been shown to be sensitized to pancreatic tissue antigens. Mice immunized with homologous pancreatic islets have been found to develop glucose intolerance and insulitis. Since lymphocytes may be involved in diabetogenesis, we wished to determine if lymph node cells from islet-immunized mice can recognize and respond to islet cells in vitro.A.TL female mice were immunized with an emulsion of BALB/c islet homogenate and complete Freund's adjuvant (CFA); sham-treated A.TL mice were injected with adjuvant and water. Mice were sacrificed 7\p=n-\8 days later and the draining lymph nodes were removed. The lymph node cells were co-cultured with freshly prepared irradiated BALB/c islet cell, which served as stimulator cells. The co-cultures were incubated for 24\p=n-\26h at 37\ s=deg\ C, followed by a 16 h [3H]thymidine (TdR) pulse. A significant proliferation of lymph node cells from islet-primed mice was induced during the in vitro stimulation with irradiated islet cells when compared with lymph node cells from sham-treated mice (P <0. 0 0 1 ) .The response may be islet-cell-specific, since irradiated lymph node cells from BALB/c mice failed to proliferative response under the same culture conditions (P > 0.80).

show abstract

Section: Discussionsupporting

confidence: 94%

In vitro lymphocyte recognition of islet cells following in vivo priming with allogeneic murine pancreatic islets

Scott¹,

MacKay²,

Lernmark³

1984

Acta Endocrinologica

View full text Add to dashboard Cite

show abstract

“…Whole liver or NK1.1 cell-depleted liver cells (1 × 10 5 ) from T1D C57BL/6 mice were cultured with 10 pancreatic islets from BALB/c mice in 12-well plates with RPMI 1640 (Gibco) containing 10% heat-inactivated fetal bovine serum (Gibco) at 37 °C in a humidified 5% CO 2 atmosphere for three days6364. To some wells, anti-IL-22 (eBiosciences, clone: IL22JOP), anti-NKG2A (eBiosciences, clone: 20d5) antibody or isotype control antibody (eBiosciences, clone: eBR2a) (1.5 μg ml −1 ) were added on day 0.…”

Section: Methodsmentioning

confidence: 99%

A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice

et al. 2016

View full text Add to dashboard Cite

Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1+ cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1+ cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1+ cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts. Vaccination of T1D mice with a CpG oligonucleotide TLR9 agonist (ODN 1585) enhances expansion of IL-22-producing CD3-NK1.1+ cells in the liver and prolongs allograft survival. Our study identifies a role for liver NK1.1+ cells, IL-22 and CpG oligonucleotides in the induction of tolerance to islet allografts in the liver parenchyma.

show abstract

“…Islet preparations were allowed to incubate at 370C in tissue culture medium 199 with 15% fetal bovine serum under 95% air/5% CO2 for [16][17][18] h with two to three medium changes. This method results in relative enrichment of islets because much of the exocrine tissue undergoes autolysis and islet harvesting is facilitated (14). The purity of a representative islet preparation was evaluated by the insulin/amylase ratio as described by Matas et al after overnight culture in Medium 199 (glucose 5.5 mM) and was found to be 67 ,g insulin per milligram amylase (11).…”

Section: Superoxide Dismutase Derivatizationsmentioning

confidence: 99%

Protective Role of Superoxide Dismutase against Diabetogenic Drugs

Gandy¹,

Buse²,

Crouch³

1982

J. Clin. Invest.

125

View full text Add to dashboard Cite

A B S T R A C T Copper-zinc superoxide dismutase (SOD) is present in relatively high concentrations in the ,-cells of human islets. The activity of the extracted enzyme is partially inhibited upon incubation with the diabetogenic drugs alloxan, streptozotocin, or Vacor. The role of this enzyme in protecting a-cells against chemically induced diabetes was further investigated.Incubation of intact canine islets with alloxan (0.2 mg/ml) and 4 mM glucose decreased the insulin secretory response by 87% during subsequent exposure to 28 mM glucose. Concomitantly the SOD-specific activity (units of enzyme activity per milligram immunoreactive SOD) decreased 50% in alloxan-exposed islets. When islets were protected from alloxan toxicity by including 28 mM glucose with alloxan, the insulin secretory response and SOD specific activity remained identical to controls. Thus, SOD specific activity correlates with maintenance of ,B-cell function.To test the effectiveness of SOD against streptozotocin in vitro, canine islets were incubated 10 min with or without streptozotocin (0.1 mg/ml) with 4 mM glucose; their functional integrity was tested subsequently as the insulin secretory response to 28 mM glucose. Exposure to streptozotocin alone decreased the response by 70%; inclusion of SOD (1.5 mg/ml) before and during exposure to streptozotocin completely prevented this effect. Cyanide-inactivated SOD was not effective.The potential of SOD to prevent streptozotocin-induced diabetes was tested in rats in vivo. SOD injected 10 s or 50 min before streptozotocin prevented or significantly attenuated diabetes. Injection of SOD and streptozotocin simultaneously was much less effective, and cyanide-inactivated SOP was ineffective. No protection was afforded by injection of SOD 12 or 24 h before streptozotocin.

show abstract

Responses of Canine Lymphocytes to Allogeneic and Autologous Islets of Langerhans in Mixed Cell Cultures

Cited by 14 publications

References 26 publications

In vitro lymphocyte recognition of islet cells following in vivo priming with allogeneic murine pancreatic islets

In vitro lymphocyte recognition of islet cells following in vivo priming with allogeneic murine pancreatic islets

A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice

Protective Role of Superoxide Dismutase against Diabetogenic Drugs

Contact Info

Product

Resources

About