A ROLE FOR CD4(-LYMPHOCYTES AS MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II INDEPENDENT HELPER-CELLS IN THE GENERATION OF CD8(+) EFFECTOR FUNCTION AGAINST INTRACELLULAR INFECTION()NK1.1(+)T T)

Major histocompatibility complex (MHC) class II (A beta) knockout mice were vaccinated with ts-4, an attenuated mutant strain of Toxoplasma gondii, which ill normal animals induces strong T cell immunity mediat ed by interferon gamma (IFN-gamma). After challenge with the lethal pa rasite strain RH, the knockout mice displayed decreased resistance con sistent with absence of CD4(+) effecters. Nevertheless, these animals generated. CD8(+) lymphocyte effectors capable of mediating partial pr otection through IFN-gamma secretion. Morever, in vivo neutralization experiments indicated that the development of resistance in knockout m ice depends on CD4(+) cells as well as interleukin 2 (IL-2). The ident ity of the IL-2-producing protective cell population was further chara cterized as CD4(+), NK1.1(+) by in vitro depletion studies and reverse transcriptase-PCR analysis of fluorescence-activated cell sorter (FAC S)-purified CD4(+)NK1.1(+) T lymphocytes. These results demonstrate th at in the absence of conventional MHC class II-restricted CD4(+) T lym phocytes, CD8 printing persists and mediates partial protective immuni ty to T. gondii. Moreover, the data argue that CD4+, NK1.1(+) cells, p reviously implicated in the initiation of T helper cell 2 (Th2) respon ses through their production of IL-4, can also play a role as alternat ive IL-2-secreting helper cells in Th1-mediated host resistance to inf ection.