DISTINCT CD4(-CELL HELPER REQUIREMENTS IN THEILERIA PARVA-IMMUNE AND PARVA-NAIVE BOVINE CTL PRECURSORS() T)

There is strong evidence that class I MHC-restricted parasite-specific CD8(+) CTL protect cattle against the protozoan parasite Theileria pa rva, As part of an effort to develop a subunit vaccine for the inducti on of these responses, we have investigated the factors involved in th e generation of T. parva-specific CTL in cattle, Purified populations of bovine immune and naive CD8(+) T cells were cocultured with autolog ous T parva-infected lymphoblasts (TpL) in the presence or absence of immune CD4(+) T cells or cytokine preparations, Neither population dev eloped CTL activity when cultured with TpL alone, whereas incorporatio n of immune CD4(+) T cells in the cultures supported the generation of parasite-specific CTL from both immune and naive CD8(+) precursors, T he helper function of parasite-specific CD4(+) T cells for immune, but not naive, CTL precursors could be replaced by CD4(+) T cells respond ing to an unrelated Ag or by the addition of T cell growth factors or recombinant bovine IL-2, In experiments with two-chamber culture plate s, in which cocultures of CD4(+) and CD8(+) T cells with TpL were sepa rated by a semipermeable membrane, CTL activity was observed to develo p only in immune precursor populations, Hence, although bovine T. parv a-specific CD8(+) memory T cells need no helper signals other than IL- 2 for activation, their naive counterparts require close contact with responding parasite-specific CD4(+) T cells. This may reflect essentia l receptor-ligand interactions, or alternatively, a requirement for mo re stringent microenvironmental cytokine conditions.