Vitamin C Supplementation Reconstitutes Polyfunctional T Cells in Streptozotocin-Induced Diabetic Rats

Eur J Nutr. 2012 Aug;51(5):623-33. doi: 10.1007/s00394-011-0176-5. Epub 2011 Feb 25.


Background: Studies have demonstrated that vitamin C supplementation enhances the immune system, prevents DNA damage, and decreases the risk of a wide range of diseases. Other study reported that leukocyte vitamin C level was low in diabetic individuals compared with nondiabetic controls.

Aim of the work: To study the effect of vitamin C on oxidative stress, blood lipid profile, and T-cell responsiveness during streptozotocin (STZ)-induced type I diabetes mellitus.

Methods: Thirty male Sprague-Dawley rats were randomly split into three groups. The first served as a control group (n = 10) in which rats were injected with the vehicle alone. The second (n = 10) and the third groups (n = 10) were rendered diabetic by intraperitoneal (i.p.) injection of single doses of STZ (60 mg/kg body weight). The third group was supplemented with vitamin C (100 mg/kg body weight) for 2 months.

Results: T lymphocytes from the diabetic rats were found to be in a stunned state, with a decreased surface expression of the CD28 costimulatory molecule, low levels of phosphorylated AKT, altered actin polymerization, diminished proliferation and cytokine production, and, eventually, a marked decrease in abundance in the periphery. Vitamin C was found to significantly decrease the elevated levels of blood hydroperoxide, glucose, cholesterol, triglycerides and low-density lipoprotein (LDL) in diabetic rats. Furthermore, it was found to restore CD28 expression, AKT phosphorylation, actin polymerization, and polyfunctional T cells (IFN-γ- and IL-2-producing cells that exhibit a high proliferation capacity).

Conclusion: Vitamin C treatment restores and reconstitutes polyfunctional, long-lived T cells in diabetic rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants
  • Ascorbic Acid / administration & dosage*
  • Blotting, Western
  • CD28 Antigens / genetics
  • CD28 Antigens / metabolism
  • Cell Proliferation / drug effects
  • DNA Damage / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dietary Supplements*
  • Down-Regulation
  • Immune System / drug effects
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Lipoproteins, LDL / blood
  • Male
  • Oxidative Stress / drug effects
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Risk Factors
  • Signal Transduction
  • Streptozocin / adverse effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Triglycerides / blood
  • Vitamins / administration & dosage*


  • Antioxidants
  • CD28 Antigens
  • Interleukin-2
  • Lipoproteins, LDL
  • Triglycerides
  • Vitamins
  • Streptozocin
  • Interferon-gamma
  • Ascorbic Acid