Burn injury induces the expression of cystine/glutamate transporter (x(c)(-)) in mouse T cells

Immunol Lett. 2009 Aug 15;125(2):137-44. doi: 10.1016/j.imlet.2009.06.011. Epub 2009 Jul 2.


System x(c)(-) transporter, formed by the association of CD98 and xCT proteins, regulates the import of cystine into cells and is poorly expressed in T lymphocytes. Thermal injury is associated with high oxidative stress, decreased levels of glutathione (GSH) and protein deficiency, all described as promoters of xCT expression and system x(c)(-) activity. T cell dysfunction is a consequence of thermal injury and has been related to oxidative stress. In order to evaluate if thermal injury induced system x(c)(-) expression in splenic T lymphocytes, cells were isolated from sham- and burn-injured mice at day 10 post-burn and cultured in 2-mercaptoethanol (2-ME)-rich and -free media. Isolated splenic T cells were stimulated and cell proliferation, system x(c)(-) expression and cystine transport activity were measured. Our results demonstrate that only burn-injured T cells express xCT and proliferate in (2-ME)-free media. In these cells, viability and CD25 expression was higher than control T cells. x(c)(-) system expression was responsible for significantly higher (14)C-cystine uptake by burn-injured T cells and its inhibition by sulfasalazine (SASP) decreased significantly their proliferation. Overall, these results demonstrate that xCT expression is induced by thermal injury in T lymphocytes and that cystine import by x(c)(-) leads to T cell dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System y+ / genetics
  • Amino Acid Transport System y+ / immunology
  • Amino Acid Transport System y+ / metabolism*
  • Animals
  • Biological Transport, Active / drug effects
  • Burns / genetics
  • Burns / immunology*
  • Burns / metabolism
  • Burns / pathology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cystine / metabolism*
  • Fusion Regulatory Protein-1 / metabolism
  • Gene Expression Regulation
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Protein Binding
  • Spleen / pathology
  • Sulfasalazine / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology


  • Amino Acid Transport System y+
  • Fusion Regulatory Protein-1
  • Interleukin-2 Receptor alpha Subunit
  • Slc7a11 protein, mouse
  • Sulfasalazine
  • Cystine