Theileria parva: reappearance of schizonts in infected lymphoblastoid cells treated with parvaquone is dependent on interleukin 2-like growth factors.

Schizont-infected cell lines derived by in vitro infection of bovine T cell clones with the Muguga isolate of Theileria parva were treated for 72 hr with the theileriacidal drug, parvaquone, at a concentration of 10 micrograms/ml. This treatment completely eliminated schizonts from the recovered cells, which failed to undergo further proliferation and died. However, treated cells cultured with either bovine T cell growth factor or human recombinant interleukin 2 remained viable, underwent proliferation, and in many instances, schizonts reappeared. When cultured in the presence of supernatant obtained from an actively growing T. parva-infected cell line, treated cells did not proliferate, but schizonts reappeared. The cells became transformed by the parasite and grew continuously in the absence of exogenous growth factor. The appearance of schizonts was preceded by the development of densely staining intracytoplasmic inclusions, visualized by light and electron microscopy. Electron-dense inclusions were shown to contain DNA. Hybridization of a T. parva-specific DNA probe to Southern blots of restriction enzyme-digested DNA prepared from parvaquone-treated cells which developed inclusions but not schizonts produced a pattern similar to that seen with DNA prepared from schizont-infected cells. We conclude that reorganization of schizonts can occur in T. parva-infected T lymphocytes cured of infection with parvaquone in the presence of interleukin 2 or growth factors produced by T. parva-infected cells. The implications of these results for the establishment of a carrier state following parvaquone therapy are discussed.