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.