(995) Adoptive Transfer of Diabetic CD4+ T-cells into normal pregnant rats induces characteristics of gestational diabetes

Gestational diabetes mellitus (GDM) is characterized by hyperglycemia, β-cell dysfunction, and insulin sensitivity during pregnancy, and is associated with increased T cell activation. We hypothesize, CD4+ T cells play a role in the pathophysiology of GDM by stimulating antibodies leading to β-cell destruction causing glucose intolerance, renal injury and hypertension during pregnancy.

Study Design:

Splenic CD4+ T cells were magnetically separated from virgin streptozotocin (STZ)-induced diabetic female Dahl Salt Sensitive (SS) rats (DM-CD4+ T cells) and virgin female Dahl SS rats (SS-CD4+ T cells) and injected into normal pregnant Sprague Dawley (NP-SD) rats on gestational day (GD) 12. On GD18, rats were placed in metabolic cages overnight for urine collection to determine proteinuria, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated-lipocalin (NGAL). On GD 19, mean arterial pressure (MAP), Glucose Tolerance Test (GTT), and blood glucose levels were measured. A one-way ANOVA was used for statistical analysis.

Results: On GD19, MAP was increased in DM-CD4+ T cell recipients (101±1 mmHg, n=8, p< 0.05) and SS-CD4+ T cell recipients (110±4 mmHg, n=6, p< 0.05) compared to NP-SD controls (95±2 mmHg, n=7). Blood glucose was elevated in DM-CD4+ T cells rats (132 ± 6 mg/dl, n=7, p< 0.05) compared to SS-CD4+ T cells rats (102±3 mmHg, mg/dl, n=5) and NP-SD rats (84 ± 4 mg/dl, n=7). GTT was impaired in DM-CD4+ T cell rats versus other groups. Protein excretion increased in DM-CD4+ T cell rats (8± 1 ml/day) versus SS-CD4+ T cell rats (3±0.5 ml/day) and NP-SD rats (4 ± 1 ml/day). Urinary KIM-1 and NGAL were increased in DM-CD4+ T cell rats (55 ± 23 pg/day; 40 ± 7 ng/day, p< 0.05) compared to SS-CD4+ T cell rats (11 ± 7 pg/day;20 ± 7 ng/day) and NP-SD rats (18 ± 1 pg/day; 22 ± 1 ng/day).

Conclusion: These data indicate CD4+ T cells cause characteristics of GDM such as increased glucose, renal injury and HTN during pregnancy in association with placental dysfunction, demonstrating the importance of CD4+T cells in causing the pathophysiology of GDM.