Pteridines are produced during interleukin 2-induced T-cell proliferation and modulate transmission of this signal

Pteridine levels of interleukin 2 (IL-2) receptor+ T-cell populations have been determined by HPLC after iodine oxidation; neopterin was monitored in the culture supernatants by radio-immunoassay. Upon addition of IL-2, cellular levels of biopterin and 6-hydroxymethylpterin rise transiently from 0.02 to 0.9 pmol/10(6) cells, cellular levels of neopterin from 1.5 to 4.1 pmol/10(6) cells. They peak at 8 and 13 h, respectively, after exposure to IL-2. Neopterin is not accumulated in the culture supernatant. DNA synthesis in T cells begins 10-12 h after adding the lymphokine and the portion of cells that undergo S-phase transition gradually increases during the subsequent 10 h. Entry into DNA synthesis phase is markedly accelerated if IL-2 is supplied together with tetrahydrobiopterin (0.8-1.6 X 10(-6) M) and the kinetics of entry into the S-phase transition during the period of 6-20 h become linear. This indicates that tetrahydrobiopterin modulation of IL-2 activity (Ziegler, I. et al. Naturwiss 72 (1985) 330) is an early event occurring during IL-2 signal transmission.