The amino acid arginine is indispensible for the host's T cell response against tumors or chronic infection. Without arginine, a T cell receptor (TCR) component cannot be produced efficiently, thus dampening TCR signaling. As a result, the cells do not proliferate normally or produce the survival cytokine IL-2, although they still make inflammatory cytokines such as IFNγ and TNF.
Das et al. now find that CD8+ T cells in the livers of patients with chronic hepatitis B infections show signs of arginine starvation. Despite proliferating poorly, the cells' production of IFNγ and TNF might explain the liver damage seen in these patients. The amino acid deficiency stemmed from the activity of the arginine-destroying enzyme arginase, which was elevated in inflamed livers. The arginase source is still unknown but seems to be confined to the liver, as T cells elsewhere in the patients were less affected.
Culturing patients' liver-derived CD8+ T cells with arginine corrected their defects. Whether arginine supplements can help cure hepatitis B remains to be seen.