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All cells depend on nutrients acquired from the extracellular environment to support the biochemical processes required for cell growth. Although unicellular organisms such as bacteria and yeast have developed strategies to survive nutrient limitation, the growth of these organisms is constrained by nutrient availability. In contrast, mammalian cells exist in a nutrient-rich environment where cell growth is not limited by substrate availability, but rather by the levels of extrinsic growth factors (1, 2). Because of the limits imposed by growth factor control, cellular proliferation is restricted even under nutrient conditions that are highly favorable for unlimited cell growth. However, it is becoming apparent that nutrient availability also plays an important role in controlling mammalian cell growth. An example of this form of growth control is found in the work of Angelini et al. (3) reported in this issue that describes how dendritic cells control the proliferation of T cells by regulating the availability of the amino acid cysteine. Previous studies in lymphocytes identified cysteine as rate limiting for cell growth and proliferation after antigen receptor engagement (4). Cysteine and cystine, the free thiol- and disulfide-bonded forms of the amino acid, respectively, exist in an equilibrium defined by redox conditions. In the oxidizing environment of the extracellular space, the cysteine equivalents exist primarily in the form of cystine (5). In contrast, a reducing environment is maintained intracellularly, and thus the cysteine within the cell exists predominantly in the free thiol form (6). Cystine and cysteine are not taken up by the same amino acid transporter but require the expression of distinct transport systems (7). Despite the limited amount of cysteine in the plasma, lymphocytes do not express the cystine transporter and cannot take up cystine (7, 8). Furthermore, although cysteine is not generally considered an essential amino acid, lymphocytes …

Antigen-presenting cells control T cell proliferation by regulating amino acid availability