Burn injury induces the expression of cystine/glutamate transporter (x(c)(-)) in mouse T cells.
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.
D'Elia
Michele
M
Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Québec, Canada.
Patenaude
Julie
J
Dupras
Charles
C
Bernier
Jacques
J
D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002056:Burns / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003553:Cystine / Q000378:metabolism*; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D005786:Gene Expression Regulation; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011485:Protein Binding; D013154:Spleen / Q000473:pathology; D012460:Sulfasalazine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D027182:Amino Acid Transport System y+; D027261:Fusion Regulatory Protein-1; D053645:Interleukin-2 Receptor alpha Subunit; C492255:Slc7a11 protein, mouse; D012460:Sulfasalazine; D003553:Cystine