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