A growth-inhibitory substance found in the culture of a B-precursor
leukemia cell line, NALM-20, was purified from the serum-free culture medium and identified as
arginine deiminase derived from Mycoplasma arginini (EC 3.5.3.6).
Arginine deiminase strongly inhibited, in a dose-dependent manner, the growth of human T cells and T lymphoblastoid cell lines, but not that of B-precursor and myeloid cell lines. The addition of
L-arginine completely restored the growth of T lymphoblastoid cells that had been inhibited by
arginine deiminase. The addition of L-
ornithine also partially restored it. This
enzyme suppressed
interleukin-2 (IL-2) production and
IL-2 receptor expression in T cells stimulated by non-specific
mitogens. The morphologic features of dying cells and DNA fragmentation indicated that
arginine deiminase induced apoptotic cell death in T lymphoblasts. Cell cycle analysis revealed that G1-->S transition was blocked in cell treated with
arginine deiminase, accompanied by the increase of apoptotic nuclei in the sub-G1 fraction. In conclusion, the deletion of the essential nutrient
L-arginine by
arginine deiminase significantly inhibited cell growth and activation in T lymphoblasts, accompanied by the induction of apoptotic cell death.