Activated human CD4+ T cells express transporters for both cysteine and cystine

Abstract

Because naïve T cells are unable to import cystine due to the absence of cystine transporters, it has been suggested that T cell activation is dependent on cysteine generated by antigen presenting cells. The aim of this study was to determine at which phases during T cell activation exogenous cystine/cysteine is required and how T cells meet this requirement. We found that early activation of T cells is independent of exogenous cystine/cysteine, whereas T cell proliferation is strictly dependent of uptake of exogenous cystine/cysteine. Naïve T cells express no or very low levels of both cystine and cysteine transporters. However, we found that these transporters become strongly up-regulated during T cell activation and provide activated T cells with the required amount of cystine/cysteine needed for T cell proliferation. Thus, T cells are equipped with mechanisms that allow T cell activation and proliferation independently of cysteine generated by antigen presenting cells.

Amino Acids and Immune Response: A Role for Cysteine, Glutamine, Phenylalanine, Tryptophan and Arginine in T-cell Function and Cancer?

“…In lymphocytes, cysteine has been identified as rate limiting for cell growth and proliferation with a series of studies demonstrating a role for cysteine in regulating the proliferation of T-cells [21][22][23][24][25][26]. Redox conditions determine the equilibrium between the levels of cysteine (free thiol form) and cystine (disulfide bonded form).…”

T cell metabolism drives immunity

“…The alanine serine and cysteine transporter system (ASCT2/ Slc1a5), which also transports glutamine, is another solute carrier whose expression increases after T cell activation (Levring et al, 2012). It was recently found that loss of ASCT2 decreased glutamine import and impaired OXPHOS and glucose metabolism in activated CD4 T cells (Nakaya et al, 2014).…”

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

“…The GSH system is also necessary for efficient lymphocyte proliferation. Notably, cystine, the rate-limiting factor in GSH biosynthesis, is supplied to lymphocytes during their encounter with DCs (28,29) and, upon activation, is taken up from the medium through the cystine/glutamate antiporter x c - (30). GSH facilitates the proliferation of T lymphocytes (23) and is necessary for their G 1 /S transition (31).…”